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Melphalan is an alkylating agent used in both autologous (ASCT) and allogeneic stem cell transplantation. It is a substrate of L-type amino acid transporter-1 (LAT-1) and LAT-2, which are involved in its tissue penetration and elimination. Gabapentin and pregabalin, common concomitant medications in patients with multiple myeloma undergoing ASCT, are also substrates of LAT transporters, raising concern for potential competitive inhibition of melphalan transport. We evaluated whether concurrent use of gabapentin or pregabalin in patients receiving high-dose melphalan (≥140 mg/mWe aimed to determine if concurrent administration of gabapentin or pregabalin and melphalan increased melphalan toxicity.This was a single-center, retrospective evaluation including patients ≥18 years of age who received high-dose melphalan as part of a conditioning regimen at the Winship Cancer Institute of Emory University between August 1, 2010 and April 1, 2020 and were followed through their transplant admission. After identification and inclusion of patients who received melphalan in combination with gabapentin or pregabalin, patient matching based on age (±5 years), sex, and melphalan dose (140 mg/mAmong 176 patients evaluated in each group, median hospital LOS was 16 days, median time to neutrophil engraftment was 14 days, and median time to platelet-20 engraftment was 16 days in both groups. In addition, there were no significant differences in supportive care requirements between groups.In this study, use of gabapentin or pregabalin in combination with melphalan did not impact safety of the conditioning regimen in patients undergoing ASCT.

Background: Despite significant advances in therapeutic options for multiple myeloma (MM) patients, there is an ongoing need to identify effective treatment strategies in the relapsed space. The efficacy of daratumumab, pomalidomide and dexamethasone (DPD) in relapsed and/or refractory patients has been demonstrated in clinical trials, but there is limited data at first relapse in a real world setting. Here, we present a retrospective analysis utilizing our institutional data of multiple myeloma patients treated with DPD at first relapse at the Winship Cancer Institute of Emory University. Methods: Ninety relapsed and/or refractory myeloma (RRMM) patients were identified who had received only one prior line of therapy and subsequently treated with DPD at first relapse. Dose-adjustments were made based on the treating physician's discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61.9 years (range, 38-85). Other notable patient characteristics include: M/F 44.4%/55.6%; W/AA/Asian 50%/46.7%/3.3%; ISS I/II/III 28.9%/31.1%/20%; Isotype IgG/IgA/FLC 62.2%/17.8%/16.7%; standard risk/high risk 21.1%/52.2%. High risk disease was defined as the presence of t(4;14), t(14;16), del(17p), and/or complex karyotype. A total of 69 patients (76.7%) underwent autologous stem cell transplant (ASCT) upfront after attaining at least a partial response with induction therapy. The most common induction regimen was RVD (78.9%). 81.1% of patients received maintenance therapy, with 50.5% receiving single-agent lenalidomide maintenance and 72.2% receiving a lenalidomide-based maintenance regimen (RVD: 8 pts; Rd: 4 pts; IRD: 7 pts, KRD: 1 pt). With a median follow up of 72 months, the median OS from diagnosis was 158.6 months (95% CI 126.7-190.5) for the entire cohort. The median PFS from time of initiation of DPD was 15.6 months (95% CI 9.9-21.2), and the median OS from time of initiation of DPD was 41.3 months. For high risk vs standard risk patients, the mPFS from time of initiation of DPD was 7.2 months (95% CI 3.6-10.7) vs 17.6 months (95% CI 10.9-24.3), respectively. Median PFS2 in patients 2 years from transplant was 8.6 months vs NR, respectively. Conclusions: These results illustrate the activity of DPD at first relapse in a predominantly len-refractory RRMM cohort of patients with impressive long-term outcomes. This benefit was particularly demonstrated in patients with time to relapse of >2 years post-transplant. Figure 1 Figure 1. Disclosures Joseph: GSK: Honoraria; BMS: Research Funding; Takeda: Research Funding; Karyopharm: Honoraria. Boise: AstraZeneca: Honoraria, Research Funding; AbbVie/Genentech: Membership on an entity's Board of Directors or advisory committees. Hofmeister: BlueBird Bio: Other: Non-CME speaker; Aptitude Health: Other: Non-pharma speaker for education, research, marketing; Verascity: Other: Non-pharma speaker for education, research, marketing; TRM Oncology: Other: Non-pharma speaker for education, research, marketing; DAVA Oncology: Other: Non-pharma speaker for education, research, marketing; Medscape: Other: Non-pharma speaker for education, research, marketing; Amgen: Other: Non-CME speaker; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Philips Gilmore: Other: CME speaker; Non-pharma speaker for education, research, marketing; BioAscend: Other: CME speaker; Imbrium: Membership on an entity's Board of Directors or advisory committees; Myeloma360: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Local PI of CST; Oncolytics: Other: National PI for CST; PI or co-PI IST; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; BMS/Celgene: Other: National PI for CST; PI or co-PI IST; Local PI of CST; Sanofi: Other: National PI for CST; PI or co-PI IST; Ohio State University: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: IP rights, Patents & Royalties. Kaufman: Incyte, TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sutro, Takeda: Research Funding; Roche/Genetech, Tecnopharma: Consultancy, Honoraria; Fortis Therapeutics: Research Funding; Heidelberg Pharma: Research Funding; BMS: Consultancy, Research Funding; Amgen: Research Funding; Tecnofarma SAS, AbbVie: Honoraria; Incyte, celgene: Consultancy; Janssen: Honoraria; Novartis: Research Funding; Genentech, AbbVie, Janssen: Consultancy, Research Funding. Lonial: Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Merck: Honoraria; AMGEN: Consultancy, Honoraria. Nooka: GlaxoSmithKline: Consultancy, Other: Travel expenses; Amgen: Consultancy, Research Funding; Oncopeptides: Consultancy; Janssen Oncology: Consultancy, Research Funding; Sanofi: Consultancy; Karyopharm Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Adaptive technologies: Consultancy.

Study objectives Immune checkpoint inhibitors have produced durable responses across a variety of cancers. Although programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors activate T cells against tumor cells, they may also cause autoimmune-like toxicities termed immune-related adverse events (irAEs). Although much is known regarding irAEs that occur early during treatment, data on the long-term toxicity profile of these agents are more limited. Our primary objective was to evaluate the frequency of patients receiving anti-PD-1/PD-L1 therapy for at least 6 continuous months who experienced new or worsening irAEs requiring clinical interventions. Secondary objectives included assessment of other factors associated with clinically significant irAEs after at least 6 months of therapy. Design Retrospective chart review. Setting Large university-affiliated National Cancer Institute-designated comprehensive cancer center. Patients A total of 159 adults diagnosed with any malignancy who received a PD-1/PD-L1 inhibitor-nivolumab, pembrolizumab, or atezolizumab-as monotherapy or with concurrent cytotoxic agents, for at least 6 months, between January 1, 2014, and September 1, 2017. Measurements and main results We collected information on the incidence and timing of irAEs, along with patient demographics and other treatment outcomes. Thirty-eight patients (24%) experienced clinically significant, new, or worsening irAEs after 6 months of treatment with anti-PD-1/PD-L1 therapy. Hypothyroidism was the most common irAE experienced (20 patients [12.6%]), followed by pneumonitis (5 patients [3%]); 2 patients died due to pneumonitis. Four patients (2.5%) had a deepened disease response beyond 6 months of treatment. Conclusion Our results revealed that a significant proportion of patients continue to experience irAEs with long-term use of PD-1/PD-L1 inhibitors. These results further contribute to the risk-benefit understanding of chronic PD-1/PD-L1 antagonism and support discontinuation of these agents following deepest response.

Introduction Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse. Patients and Methods We evaluated 112 patients diagnosed with DLBCL from 2009 to 2016 at Emory Healthcare and classified them as high (n = 44) or low risk (n = 68) for CNS relapse and compared CNS prophylaxis rates and relapse rates between groups. The primary outcome was to compare the CNS relapse rate in high-risk patients who received intrathecal prophylaxis with patients who did not. Results Twenty-six patients (14 high-risk and 12 low-risk) received intrathecal prophylaxis. Only 4 of 112 patients experienced a CNS relapse, including 1 in the high-risk group and 3 in the low-risk group. Among 14 high-risk patients who received intrathecal prophylaxis, no patient experienced CNS relapse compared with 1 of 30 high-risk patients without prophylaxis (P = 1.0). Conclusion Given the low rates of CNS relapse in this series, it is difficult to discern the impact of current risk stratification combined with intrathecal prophylaxis on outcomes. Our observation that many high-risk patients did not receive prophylaxis, whereas many low-risk patients received prophylaxis emphasizes the need for a standardized approach.

Secondary central nervous system (CNS) relapse in aggressive non-Hodgkin lymphoma (NHL) is a dismal diagnosis with poor outcomes. While prophylaxis against secondary CNS disease is recommended in patients with highly aggressive NHLs, such as Burkitt lymphoma, patients with diffuse large B-cell lymphoma (DLBCL) present a challenging clinical dilemma due to an inherently lower risk of CNS relapse. Current guidelines suggest that prophylaxis may benefit DLBCL patients at high risk for CNS relapse; however, it has been difficult to define which patients are truly at high risk. Many studies have attempted to clarify the issue, with conflicting results. Here we review current prognostic models, risk factors, and prophylaxis methods to provide a practical approach to preventing CNS relapse in patients with DLBCL.