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ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269).

Purpose:Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice.Experimental Design:This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected.Results:The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose.Conclusions:These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

Supplemental Table 1 and Supplemental Figure Legends

ABVD with or without radiation has been standard treatment for limited stage HL but carries risks of bleomycin-lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD as frontline therapy for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim PET response. Thirty-four patients with non-bulky stage I-II HL were enrolled with a median age of 36. Risk was early favorable in 53%, unfavorable in 47%. The overall and complete response rates were 100% and 97%, respectively, with a 5-year PFS of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%) and fatigue (56%). There were no cases of grade 4 neutropenia or neutropenic fever, and no patients received G-CSF. Most cases of peripheral neuropathy were grade 1 and no patients experienced grade ≥3 peripheral neuropathy. BV-AD produced a high CR rate and durable PFS with most patients requiring only 4 cycles of therapy. Compared to BV-AVD, the toxicity profile appeared improved with the omission of vinblastine, with predominantly grade 1 reversible peripheral neuropathy, and no cases of grade 4 neutropenia or neutropenic fever. This promising regimen warrants further study in Hodgkin lymphoma and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269).

PURPOSE: Reduction of chemotherapy start times (CST) and length of stay (LOS) for elective chemotherapy admissions is a priority. The aim of this project was to improve efficiency of patient care while simultaneously increasing revenue by reducing LOS and transitioning high-cost chemotherapy to the outpatient setting. METHODS: A multidisciplinary quality improvement team proposed building a new outpatient infusion suite in close proximity to the inpatient unit. This suite was then integrated into the flow of elective inpatient chemotherapy admissions and discharges for etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R). Quality measures such as CST, LOS, and revenue were used to evaluate the new infusion suite. RESULTS: In the pilot phase of the study, the average CST improved by approximately 1 hour 45 minutes ( P = .0218). The mean LOS was reduced from 4.3 to 4.1 midnights ( P = .0214). In terms of hours, LOS was reduced from 105.8 to 95.5 hours ( P < .0001). A mean quarterly revenue of $309,410 US dollars was noted during the pilot that had not been previously billed. These improvements were sustained throughout the control phase. CONCLUSION: Delays in CST and prolonged LOS lead to patient dissatisfaction and increased cost to the health care system. Focus groups and patient feedback are important when designing and implementing new workflows. The creation of an outpatient integrated infusion suite allows medical centers to meet patients' expectations of reducing number of visits while also reducing LOS and capturing new revenue. Adherence to scheduling guidelines further reduces the CST for elective chemotherapy administration.

Purpose Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in CLL. Umbralisib a novel, highly selective PI3Kδ/CK1e inhibitor, is active and well tolerated in CLL patients. This phase 2 trial evaluated umbralisib in CLL patients who are intolerant to prior BTK or PI3K inhibitor therapy. Patients and methods In this phase 2 trial (NCT02742090), umbralisib was initiated at 800 mg oral daily in CLL patients requiring therapy per investigator discretion who were intolerant to prior BTK or PI3K inhibitor therapy, until progression or toxicity. Primary endpoint was progression-free survival (PFS). Secondary endpoints included time to treatment failure and umbralisib safety profile. DNA isolated from buccal swabs was genotyped for polymorphisms in CYP3A4, CYP3A5 and CYP2D6. Results Fifty-one patients were enrolled (44 BTKi and 7 PI3Kδi intolerant). Median age was 70 years (range 48-96), median of 2 prior lines of therapy (1-7), 24% had del17p and/or TP53 mutation, and 65% were IGHV unmutated. Most common AEs leading to prior KI discontinuation were rash (27%), arthralgia (18%), and atrial fibrillation (16%). Median progression free survival (PFS) was 23.5 months (95% CI 13.1-not estimable). 58% of patients were on umbralisib for a longer duration than prior KI. Most common (≥5%) grade ≥3 AEs on umbralisib (all causality) were neutropenia (18%), leukocytosis (14%), thrombocytopenia (12%), pneumonia (12%), and diarrhea (8%). Six patients (12%) discontinued umbralisib due to an AE. Eight patients (16%) had dose reductions and were successfully re-challenged. Conclusions Umbralisib is safe and effective in this BTK and alternate PI3K inhibitor intolerant CLL population. These are the first prospective data to confirm that switching from a BTK or alternate PI3K inhibitor to umbralisib can result in durable, well tolerated responses.

Summary Background Patients with chronic lymphocytic leukaemia and high-risk features have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, to ibrutinib therapy in this population. Methods We did a randomised, phase 3, multicentre study (GENUINE) of patients aged 18 years or older with relapsed or refractory chronic lymphocytic leukaemia with at least one of 17p deletion, 11q deletion, or TP53 mutation, at 119 clinics in the USA and Israel. Eligible patients had received at least one previous chronic lymphocytic leukaemia therapy and had an Eastern Cooperative Oncology Group performance status of 2 or lower. We randomised patients (1:1) using permuted block randomisation with a block size of four and stratified by previous lines of therapy (one vs two or more) to receive ibrutinib alone or ibrutinib in combination with ublituximab. Treatment allocation was not masked to patients or investigators. Ibrutinib was given orally daily at 420 mg for all cycles. Ublituximab was given intravenously in 28-day cycles, with increasing doses during cycle 1 (≤150 mg on day 1, 750 mg on day 2, and 900 mg on days 8 and 15) and continuing at 900 mg on day 1 of cycles 2–6. After cycle 6, ublituximab was given at 900 mg every three cycles. The study was initially designed with co-primary endpoints of progression-free survival and overall response rate but due to protracted patient accrual, the protocol was amended to have a single primary endpoint of independent review committee-assessed overall response rate (defined as the proportion of patients who had a partial response, complete response, or complete response with incomplete marrow recovery according to the 2008 International Workshop on CLL criteria) in the intention-to-treat population. Safety was evaluated in the population of patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov , NCT02301156 , and the final analysis is presented. Findings 224 patients were assessed for eligibility, of whom 126 patients were enrolled and randomly assigned to receive ublituximab plus ibrutinib (n=64) or ibrutinib alone (n=62) between Feb 6, 2015, and Dec 19, 2016. After a median follow-up of 41·6 months (IQR 36·7–47·3), the overall response rate was 53 (83%) of 64 patients in the ublituximab plus ibrutinib group and 40 (65%) of 62 patients in the ibrutinib group (p=0·020). 117 patients, including 59 in the ublituximab plus ibrutinib group and 58 in the ibrutinib group, received at least one dose of treatment and were included in safety analyses. Most adverse events were grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and seven [12%] in the ibrutinib group), anaemia (five [8%] and five [9%]), and diarrhoea (six [10%] and three [5%]). The most common serious adverse events were pneumonia (six [10%] in the ublituximab plus ibrutinib group and four [7%] in the ibrutinib group), atrial fibrillation (four [7%] and one [2%]), sepsis (four [7%] and one [2%]), and febrile neutropenia (three [5%] and one [2%]). Two patients in the ublituximab plus ibrutinib group died due to adverse events (one cardiac arrest and one failure to thrive), neither of which were treatment-related. Five patients in the ibrutinib group died due to adverse events, including one cardiac arrest, one cerebral infarction, one intracranial haemorrhage, one Pneumocystis jirovecii pneumonia infection, and one unexplained death; the death due to cardiac arrest was considered to be treatment-related. Interpretation The addition of ublituximab to ibrutinib resulted in a statistically higher overall response rate without affecting the safety profile of ibrutinib monotherapy in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia. These findings provide support for the addition of ublituximab to Bruton tyrosine kinase inhibitors for the treatment of these patients. Funding TG Therapeutics.

Germline HAVCR2 mutations, recently identified in a large subset of patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). Discovery of this heritable HLH/SPTCL diathesis has expanded our understanding of a rare and molecularly heterogeneous lymphoma. Furthermore, patients with SPTCL have excellent survival unless they develop HLH. Therefore, through compiling data on SPTCL-related conditions that predispose patients to HLH, we are better able to predict which patients with SPTCL have the greatest risk of mortality. We present the first case of SPTCL with concomitant HLH and autoimmune lymphoproliferative syndrome (ALPS) in a patient who was subsequently diagnosed with familial HLH (F-HLH) attributable to a germline STXBP2 splice-site mutation. She had wild-type HAVCR2. Reports including ours show how SPTCL can evolve in the setting of an exaggerated host inflammatory response attributable to a variety of unusual underlying etiologies.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathological overlap with primary cutaneous B-cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61-year-old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B-cells colonizing germinal center follicles; however, faint CD5 and CD23 co-expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count CLL-type monoclonal B lymphocytosis (MBL). Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B-cell lymphomas presenting in the skin. This article is protected by copyright. All rights reserved.

Introduction Recent randomized trials have demonstrated the efficacy of ibrutinib-based therapy in the treatment of patients with CLL. In Alliance A041202, a higher than expected number of unexplained deaths were reported with front-line ibrutinib in a patient population aged at least 65 years compared to ECOG 1912, which included patients up to 70 years of age. Methods Therefore, we conducted a retrospective analysis to investigate whether ibrutinib was associated with a greater mortality in older patients outside of a clinical trial setting. This multicenter analysis was performed by investigators at 20 academic and community practices. Results Amongst the 391 patients included, there was no correlation between age and response rate, PFS, or OS. However, there was a trend to higher rate of deaths in patients >65-years-old (8.7% vs 3.8%, p=0.097), with an increased number of early deaths (13 vs 4, p=0.3). Conclusion These data suggest greater intolerance, and possibly mortality, with ibrutinib in an older population. Patients should be educated regarding the potential complications related to ibrutinib and symptoms of concern to report.

Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB; 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non-TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression-free survival with post-ICB treatment (median, 17.5 months vs. 6.1 months, p = .035) and longer time-to-subsequent treatment failure, defined as time from initial ICB progression to failure of subsequent treatment (median, 34.6 months vs. 9.9 months, p = .003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

IMPORTANCE: It remains unclear how the historical exclusion of women and racial and ethnic minority groups from medical training, and therefore the oncologic subspecialties, has contributed to rates of faculty diversity among oncology departments over time. Oncologic faculty diversity is an important initiative to help improve care and address health disparities for an increasingly diverse US population with cancer. OBJECTIVES: To report trends in academic faculty representation by sex and by race and ethnicity for radiation oncology (RO) and medical oncology (MO) departments and to describe comparisons with the general US population, medical students, RO and MO trainees, clinical department chairs, and faculty in other departments. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used data from the Association of American Medical Colleges to analyze trends by sex and by race and ethnicity among full-time US faculty in RO and MO departments from 1970 through 2019. Data were analyzed between October 2020 and April 2021. MAIN OUTCOMES AND MEASURES: Proportions of women and individuals from underrepresented in medicine (URM) racial and ethnic groups (Black, Hispanic, and Indigenous individuals) were calculated among RO and MO academic departments; trends were analyzed over 5 decades. These proportions were compared with cohorts already described. In addition, proportions of women and URM individuals were calculated by faculty rank among RO and MO departments. RESULTS: In 1970, there were 119 total faculty in RO (10 women [8.4%] and 2 URM [1.7%]) and 87 total faculty in MO (11 women [12.6%] and 7 URM [8.0%]). In 2019, there were 2115 total faculty in RO (615 women [29.1%] and 108 URM [5.1%]) and 819 total faculty in MO (312 women [38.1%] and 47 URM [5.7%]). Total faculty numbers increased over time in both RO and MO. Faculty representation of URM women proportionally increased by 0.1% per decade in both RO (95% CI, 0.005%-0.110%; P

Objectives The combination of lenalidomide + rituximab (R2) has shown complementary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (NHL), as well as mantle cell lymphoma (MCL), an uncommon but aggressive form of NHL. The MAGNIFY phase 3 trial previously reported an ORR of 54% in patients with R/R MCL (Sharman J, et al. Hematol Oncol. 2019). Presented here are updated analyses from this trial. Materials and methods MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL, marginal zone lymphoma, and MCL. Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m2/wk cycle 1 and then every 8 wk starting with cycle 3 (R2) is given for 12 cycles followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group (IWG) criteria. Secondary end points include safety, CR rate, duration of response (DOR), duration of CR (DOCR), time-to-response (TTR), time-to-next antilymphoma therapy, and overall survival. This analysis evaluates the interim primary endpoint of overall response rate (ORR) by 1999 IWG criteria and safety of R2 induction in patients with MCL in the induction intention-to-treat population. Results As of August 28, 2020, 73 patients with MCL were enrolled (median age, 70.0 y [range, 51–88]); 89% had stage III/IV disease, and 41% had bulky disease (> 7 cm or > 3 cm ×3 lymph nodes). All patients had received prior rituximab-containing therapy, with 25 (34%) rituximab refractory (progression ≤ 6 mo after last rituximab dose). Seven patients (10%) had received prior ibrutinib. Median follow-up was 31.7 mo for patients still alive. ORR was 51%, with 34% CR rate (CR + CRu). Response rates were similar in patients refractory to rituximab (ORR = 48%, CR/CRu = 32%) and patients not refractory to rituximab (ORR = 52%, CR/CRu = 35%). Median DOR was 31.6 mo; median DOCR was not reached; median TTR was 2.8 mo, and median PFS was 28.0 mo, with 1-year PFS rate of 57%. The most common treatment emergent adverse events (TEAEs) of any grade were neutropenia (51%), fatigue (44%), diarrhea (32%), constipation (28%), cough (28%), dyspnea (26%), and nausea (26%). Grade 3/4 neutropenia was 46%; all other grade 3/4 TEAEs were ≤ 11%. Discussion R2 is an active and tolerated regimen with durable responses among patients with R/R MCL and mostly naive to Bruton tyrosine kinase inhibitor therapy. Conclusions These results suggest that R2 should be considered as a therapeutic option for patients with R/R MCL.

Objectives Relapse is expected when treating patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL), with a shortened response associated with each relapse. Lenalidomide combined with rituximab (R2) has shown enhanced activity, with a recently reported median progression free-survival (PFS) of 39.4 months in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma, including those with FL and MZL (Augment; J Clin Oncol. 2019;37:1188). Materials and methods MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), MZL, and mantle cell lymphoma (MCL). Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m2/wk cycle 1 and then every 8 wk starting with cycle 3 (R2) is given for 12 cycles followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group criteria. Secondary end points include safety, CR rate, duration of response (DOR), duration of CR, time-to-response, time-to-next antilymphoma therapy, and overall survival. Data presented here focus on induction R2 in efficacy-evaluable patients with MZL compared with the overall population of FL grades 1–3a+MZL (not including FL grade 3b, tFL, or MCL) receiving ≥ 1 treatment with baseline/post-baseline assessments. Results As of August 28, 2020, 394 patients with FL grades 1–3a and MZL enrolled; 76 (19%) had MZL. The median age of patients with MZL was 68 years (range, 46–90), 68 (89%) had stage III/IV disease, and 72 (95%) had prior rituximab-containing therapy. Overall response rate in the MZL and overall population was 66% and 75% with 39% and 44% having a CR/CRu. Median DOR was 38.6 months (95% CI, 29.4–not reached [NR]) and NR (95% CI, 38.6–NR). The median PFS was 40.9 months (95% CI, 27.8–NR) and 41.2 months (95% CI, 38.7–NR). In the MZL population, 43 patients (57%) have completed 12 cycles of R2, and 42 (55%) have been randomized and entered maintenance. Twenty-eight patients (37%) prematurely discontinued both lenalidomide and rituximab, primarily due to adverse events (AEs; n = 11; 14%) and progressive disease (n = 6; 8%). The most common (≥ 20%) all-grade AEs were neutropenia (49%), fatigue (43%), diarrhea (37%), thrombocytopenia (24%), constipation (24%), and anemia (22%). Most common (≥ 10%) grade 3/4 AEs were neutropenia (41%; 1 patient [1%] had febrile neutropenia), thrombocytopenia (13%), and leukopenia (13%). Discussion R2 is active with a tolerable safety profile in patients with R/R MZL. The efficacy and safety profile of R2 in patient with MZL were similar to results observed in the overall MAGNIFY population. Conclusions These results suggest that R2 should be considered as a therapeutic option for patients with R/R MZL.

This Viewpoint describes the concept of race-conscious medicine in oncology.

BACKGROUND: Treatment of chronic lymphocytic leukemia (CLL) with a fixed-duration venetoclax (Ven)-based regimen is now a standard of care (SOC) option for both frontline and relapsed refractory (R/R) disease based on results of the CLL14 and MURANO trials (Fischer et al NEJM 2019, Seymour et al NEJM 2018). As fixed-duration Ven regimens are now a SOC, it is expected that an increasing number of patients (pts) will ultimately progress after Ven exposure and require additional CLL-directed therapy. While many discuss re-treatment with Ven as a subsequent treatment option, the current literature contains response data on an extremely limited number of evaluable pts (11 pts MURANO, overall response rate (ORR) 55%; 3 pts VEN 365, ORR 100%). Whether re-treatment with Ven is an acceptable option remains an important unanswered clinical question. METHODS: We conducted a multicenter, retrospective study of CLL pts treated with a Ven-based regimen (Ven1) and then re-treated with a second Ven-based regimen (Ven2) in a later line of therapy (LOT). Data were collected from 13 centers and the CLL Collaborative Study of Real-World Evidence database. CLL pts were eligible for inclusion if they were treated with a Ven-based regimen in any LOT and then re-treated with a Ven-based regimen as a later LOT. Collected data included demographics, prognostic disease characteristics, tumor lysis syndrome (TLS) risk and incidence, clinical response and reasons for treatment discontinuation (dc). The primary study endpoint was investigator-assessed ORR (CR: complete response, PR: partial response, SD: stable disease, PD: progression of disease, iwCLL 2018). Kaplan-Meier method was used to estimate progression free survival (PFS). All other analyses were descriptive. RESULTS: We identified 25 pts who were re-treated with Ven. Pt characteristics prior to treatment with Ven1 are summarized in Table 1. In 24% of pts (n=6), Ven1 was administered as part of a clinical trial. Median prior LOT was 2 (range 0-10) with 12.0% treatment naïve and 60% with prior BTKi exposure. The majority of pts had ≥1 high-risk prognostic marker: del17p (39%), TP53 mut (27%), complex karyotype ≥5 abnormalities (30%) and unmutated IGHV (84%). For Ven1, treatment regimens, TLS risk, and dose are summarized in Table 2. With a median duration of exposure of 15 months (mos) (64% pts > 12 mos) for Ven1, the ORR was 88% (CR: 48%, PR: 40%, Figure 1A). Ten pts had minimal residual disease (MRD) assessments by flow cytometry; 8 pts (80%) achieved undetectable MRD (10^-4). Most common reasons for Ven1 dc included: toxicity (28%), completion of planned therapy (24%), MD/pt preference (24%), other (12%), alloHSCT (4%) and cost (4%). There was a median of 8.7 mos (36% > 12 mos) between Ven1 and the initiation of Ven2, and 88% did not receive another LOT between Ven1 and Ven2. Reasons for Ven2 initiation were either CLL progression (87.5%) or MRD-positive relapse (12.5%). For Ven2, TLS risk, TLS incidence and dose information are outlined in Table 2. TLS was a rare event during Ven re-treatment (4.5%, lab only). For Ven2, Ven monotherapy was the most common regimen (52%). Standard Ven dose-escalation was used for re-initiation in 17 of 19 pts with available data, however 1 pt started Ven2 at 400 mg daily (no TLS) and another underwent a prolonged ramp-up period. At the time of this analysis, 18 pts had available response assessments for Ven2: ORR is 72.2% (CR: 4, PR: 9, SD: 4 and PD: 1, Figure 1B). Median time from Ven2 to progression or last follow up is 8 mos (0.2-29 mos). Median PFS has not been reached. Estimated 12-month PFS is 69.1%. For pts with a CR to Ven2, median follow up time is 14.5 mos vs 7 mos for pts with PR or SD. Of 25 pts re-treated with Ven, 68% remain on Ven2 presently and 32% have discontinued Ven2, including due to CLL progression (n=4), completion of planned therapy (n=1), unrelated death (n=1), MD/pt preference (n=1). CONCLUSIONS: To our knowledge, this is the largest reported cohort of CLL pts re-treated with Ven after a prior Ven-based regimen. The high ORR in this pt population (median 2 prior therapies) suggests that re-treatment is a promising strategy and should be considered in treatment sequencing algorithms. Notably, pts with a CR to Ven2 had a longer median follow up than those with a PR or SD, suggesting a likelihood of deeper responses with time. Given the promising ORR, further research to prospectively validate Ven re-treatment is warranted. Updated data will be presented. Disclosures Allan: Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria; Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzoor:Abbvie: Current Employment, Other: may hold stock or stock options. Pu:Takeda Pharmaceuticals: Consultancy. Barr:Gilead: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Morphosys: Consultancy; TG therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy. Coombs:LOXO Oncology: Honoraria; MEI Pharma: Honoraria; Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria; Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding. Skarbnik:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy; Beigene: Speakers Bureau; Verastem: Speakers Bureau; Novartis: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CLL Society: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rhodes:Verastem: Consultancy; Abbvie/Genentech: Consultancy; Pharmacyclics: Consultancy; AstraZeneca: Consultancy. Barrientos:Janssen: Honoraria; Sandoz: Consultancy; Oncternal Therapeutics: Research Funding; Bayer: Consultancy; Genentech: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy. Roeker:American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Leslie:Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kamdar:Roche: Research Funding. Choi:Pharmacyclics/Abbvie: Research Funding; Genentech: Consultancy. Simkovic:Abbvie: Consultancy, Other: travel expenses. Lansigan:Seattle Genetics: Consultancy; BMS: Consultancy; BMS Steering Committee for MAGNIFY Program: Membership on an entity's Board of Directors or advisory committees; Spectrum Pharma: Consultancy, Research Funding. Zelenetz:Novartis: Consultancy; Gilead: Research Funding; Janssen: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech/Roche: Consultancy; Roche: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnology: Consultancy; MorphoSys: Research Funding; Amgen: Consultancy; Sandoz: Research Funding; Celgene: Research Funding; MEI Pharma: Research Funding. Moskowitz:Merck: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Miragen Therapeutics: Consultancy; Incyte: Research Funding; Merck: Consultancy; Imbrium Therapeutics, L.P.: Consultancy; Seattle Genetics: Consultancy. Goy:Morphosys: Research Funding; AbbVie: Research Funding; MD Anderson: Research Funding; Regional Cancer Care Associates/OMI: Current Employment; Infinity Verastem: Research Funding; Infinity: Research Funding; Karyopharm: Research Funding; Genentech/Roche: Research Funding; CALBG: Research Funding; Constellation: Research Funding; Bayer: Research Funding; PracticeUpdate Oncology: Consultancy; RCCA/OMI: Current Employment; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; Xcenda: Consultancy; Hackensack UMC and University of Nebraska: Research Funding. Feldman:Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Trillium: Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Furman:Verastem: Consultancy; Genentech: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Abbvie: Consultancy; TG Therapeutics: Consultancy, Research Funding; Sunesis: Consultancy; Pharmacyclics: Consultancy; Oncotarget: Consultancy; Loxo Oncology: Consultancy; Janssen: Consultancy, Speakers Bureau; Incyte: Consultancy. Mato:Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Adaptive: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding.

Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton’s tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and

Purpose: Bendamustine and rituximab (BR) has been established as a superior frontline therapy over R-CHOP in the treatment of follicular lymphoma (FL). Yttrium-90 Ibritumomab tiuxetan (90YIT) is an effective consolidation strategy after chemotherapy induction. This prospective, single-arm, multicenter, phase II trial evaluated the response rate, progression-free survival (PFS), and tolerability of BR followed by consolidation with 90YIT in patients with untreated FL. Patients and Methods: The study included grade 1 to 3a FL patients aged ≥18 years, chemotherapy-naïve, and requiring treatment for stage II–IV disease. Study treatment included an initial rituximab treatment, followed by four cycles of BR. Patients were eligible for consolidation with 90YIT, 6 to 12 weeks after BR, if they obtained at least a partial response after induction had adequate count recovery and bone marrow infiltration < 25%. Results: Thirty-nine patients were treated. Eighty-two percent had an intermediate or high-risk Follicular Lymphoma International Prognostic Index score, and 6 of 39 (15%) were grade 3a. The response rate was 94.8%, and the complete response(CR)/CR unconfirmed (CRu) rate was 77% in the intention-to-treat analysis. The conversion rate from PR to CR/Cru after 90YIT was 81%. After median follow-up of 45 months, the PFS was 0.71 (95% confidence interval, 0.57–0.89). Conclusions: This report demonstrates that four cycles of BR followed by consolidation with 90YIT achieve high response rates that are durable. In addition, consolidation with 90YIT results in a high conversion rate of PR to CR/CRu. A short course of BR followed by 90YIT is a safe and effective regimen for frontline treatment of FL.

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a rare form of non-Hodgkins lymphoma. Current frontline treatments for pcALCL include surgical resection, anthracycline-based chemotherapy, and/or radiation therapy (RT) depending on disease severity. While brentuximab vedotin (BV) has been used for refractory/relapsed cases, it recently received Food and Drug Administration (FDA) approval for use in combination with chemotherapy for peripheral T-cell lymphomas. In this case report, we utilized a combined modality therapy of RT and BV for a limited stage aggressive pcALCL presentation for which routine management is contraindicated. A 59-year-old man with a history of peripheral vascular disease (PVD) presented with an aggressive pcALCL involving the left inferior eyelid and small ipsilateral level II hypermetabolic lymph nodes at stage IIE. Due to the patient's history of PVD, the tumor's rapid growth, possible lymph node involvement, and eye proximity, BV was chosen as the initial chemotherapy treatment followed by RT. Complete metabolic resolution of the primary cutaneous lesion and lymphadenopathy was reached after BV treatment alone; complete clinical response of the primary tumor was reached following radiation therapy. Relapse occurred within 7 months. Salvage cyclophosphamide, vincristine, etoposide, and prednisone were not effective. Retreatment with BV + RT is currently being used to treat the new lesions. Our case illustrates that a combination of BV and RT can be a safe and effective initial treatment in patients with limited stage pcALCL who cannot tolerate anthracycline-based chemotherapy. Our patient had a complete response but ultimately relapsed; thus larger clinical trials are needed to better understand early-stage disease.

Purpose: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. Experimental Design: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. Results: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. Conclusions: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

LBA7564 Background: Patients with r/r B-NHL have a dismal prognosis. DIAL (Dual Immunomodulation in Aggressive Lymphoma) was a multi-center randomized phase II study testing the efficacy of nivolumab (PD-1 inhibitor) plus varlilumab (CD27 agonist) in this population. Methods: Patients were randomized (1:1) to nivolumab (240 mg IV every 2 weeks for 4 months, 480 mg IV monthly thereafter; group 1) alone or combined with varlilumab (3 mg/kg IV monthly; group 2). Cross-over (group 1 to 2) was allowed for progression. Primary endpoint was overall response (ORR) per LYRIC criteria. A sample size of 48 patients per arm would provide 80% power to detect increase in ORR from 25% to 45% using a one-sided test (p = 0.15). Pre-specified interim analysis occurred after half of the patients completed first radiologic assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Exploratory endpoints included tumor genomic assessment and immune profiling of blood and tumor. Results: 53 patients were enrolled (27 in group 1; 26 in group 2). Interim analysis included 24 patients from each arm. Mean age was 65.2 years, 34 (70.8%) were male, and 36 (75%) received prior CAR-T cell therapy. Baseline characteristics were balanced between arms. Grade ≥ 3 AEs were observed in 8 (33.3%) and 7 (30.4%) of patients in groups 1 and 2, respectively. Common AEs (> 5%) of any grade included fatigue, lymphopenia, diarrhea, rash. There were no treatment-associated deaths. Toxicity profile was similar between arms. Table summarizes efficacy outcomes. ORR was achieved in 6 patients (12.5%), not statistically different between arms; 4 responses were complete. Seven patients crossed over (1 responded after crossing). Median OS (8.6 vs 7.3 months; p = 0.39) and PFS (2.7 vs 1.4 months; p = 0.06) were similar between arms. Subgroup analysis of patients with prior CAR-T cell therapy showed similar ORR (5/36; 14%), not statistically different between arms. Correlative analysis results will be presented at conference. The trial met futility criterion on interim analysis and enrollment ceased based on pre-specified stopping rule. Conclusions: Dual immunomodulatory therapy did not enhance anti-tumor activity in patients with aggressive B-NHL compared to nivolumab alone. Response rates were low and consistent with previous data using PD-1 inhibitors in this population. Prior therapy with CAR-T cell does not seem to sensitize patients to PD-1 blockade. Toxicity profile was acceptable and dual therapy did not increase the rate of AEs. Clinical trial information: NCT03038672. [Table: see text]

Plasmacytoid dendritic cell neoplasms are aggressive and rare hematologic malignancies characterized by clonal expansion of plasmacytoid dendritic cells with frequent cutaneous involvement. The pathogenesis is not well established, and it shows enhanced expression of CD56, CD4 and CD123 detected by flow cytometry and immunohistochemistry. We report a case report of this rare disease in a hispanic child with complete remission after using a protocol for high-risk acute lymphoblastic leukemia.

Highlights • Acute myeloid leukemia can present as cholestasis with obstructive jaundice. • Extramedullary leukemia infiltration of liver can delay initiation of chemotherapy. • Hydroxyurea may be employed as a temporizing measure for effects of hyperleukocytosis., We present the case of a 55-year-old woman who presented with laboratory studies concerning for acute myeloid leukemia (AML) as well as obstructive cholestasis. In similar previously reported cases, concerns of chemotherapy toxicity exacerbated by liver dysfunction or concerns of untreated, concurrent cholecystitis in a neutropenic patient often delay initiation of chemotherapy for full medical workup. At admission, our patient was started on the cytoreductive agent hydroxyurea. By day 10 of her medical workup, her liver function had improved with total bilirubin levels normalizing. At that time, full-dose 7 + 3 induction with cytarabine and daunorubicin was then initiated.

UNSTRUCTURED As the conversation continues in addressing racial healthcare disparities nationwide not much has been written from a rural perspective. One important way to improve racial healthcare disparities in rural America is investing in training, hiring, and better supporting underrepresented minority clinicians that treat racial and ethnic minority patients in rural settings. The viewpoint will identify the problem we currently have in graduate medical education and offer suggestions for improvement.

Primary cutaneous B-cell lymphoma is a very rare entity. Skin lesions mainly occur on the lower extremities. Sheets of immunoblasts and centroblasts are characteristic findings at histologic examination. This case report highlights diagnostic and therapeutic strategies for primary cutaneous B-Cell lymphoma-leg type.

Background Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed and refractory (R/R) setting, but once discontinued due to progression or side effects, it is unclear how successful further therapies will be. Moreover, there is no data on optimal sequencing of these treatments with standard therapies and other novel agents. In a multicenter, retrospective analysis we investigated whether exposure to CBT could sensitize HL to subsequent therapy. Materials and methods Seventeen centers across the US and Canada retrospectively queried medical records for eligible patients. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment using the Lugano criteria. Secondary aims included progression free survival (PFS), duration of response (DOR), and overall survival (OS). Results Eighty-one patients were included. Seventy-two percent had stage 3-4 disease, and the population was heavily pretreated with a median of 4 therapies before CBT. Most patients (65%) discontinued CBT due to progression. The ORR to post-CBT therapy was 62%, with a median PFS of 6.3 months and median OS of 21 months. Post-CBT treatment regimens consisted of chemotherapy (44%), targeted agents (19%), immunotherapy (15%), transplant conditioning (14%), chemotherapy/targeted combination (7%), and clinical trials (1%). No significant difference in OS was found when stratified by post-CBT regimen. Conclusion In a heavily pretreated R/R HL population, CBT may sensitize patients to subsequent treatment, even after progression on CBT. Post-CBT regimen category did not impact OS. This may be a novel treatment strategy, which warrants further investigation in prospective clinical trials. Implications for practice Relapsed and refractory (R/R) Hodgkin lymphoma (HL) presents a clinical challenge, and better treatment strategies are greatly desired to prevent these patients from ultimately succumbing to their disease. The results of this multicenter analysis concur with a smaller, earlier report that checkpoint blockade therapy usage in R/R HL may sensitize patients their subsequent treatment. This approach may potentially be used to extend the number of options patients have or to bridge them to transplant. Prospective data is warranted prior to practice implementation. As more work is done in this area, we may also be able to optimize sequencing of CBT and novel agents in the treatment paradigm to minimize treatment-related toxicity and thus improve patient quality of life.