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Based on phase 3 trials, maintenance therapy after autologous stem cell transplantation (ASCT) has become the standard of care in multiple myeloma (MM). We examined the trends in maintenance therapy in a large group of patients (2530) transplanted at a single institution over two decades. Majority (n = 1958; 77%) had an ASCT within 12 months of diagnosis (early ASCT). Maintenance was employed in 39% of the patients; 42% among early ASCT and 30.5% among delayed ASCT. Most common maintenance approach was an IMiD (61%), followed by a PI (31%), or a PI + IMiD (4%). Patients with high-risk FISH received PI-based maintenance more frequently. The PFS was superior with maintenance (36 vs. 22 months, p 0.001); 37 vs. 25 months for early ASCT (p 0.001) and 29 vs. 17 months for delayed ASCT (p = 0.0008). OS from ASCT was higher with maintenance for the whole cohort at 93 vs. 73 months (p 0.001). OS from diagnosis was also better for the whole cohort with maintenance therapy, 112 vs. 93 months (p 0.001). The improvement in PFS and OS was seen in high-risk and standard risk disease. The experience with maintenance therapy post ASCT for myeloma in a non-clinical trial setting confirms the findings from the phase 3 trials.

Hematopoietic cell transplantation is increasingly used in older adults with hematological malignancies. Younger adult patients who undergo HCT have shown to commonly present with cognitive impairment and depression prior to transplant; however, little research has been done to understand the cognitive and emotional functioning of older adults undergoing HCT. This study aimed to investigate the rate of cognitive impairment in a retrospective sample of older adult HCT candidates prior to transplant using a comprehensive battery. Ninety-three patients over the age of 60 completed a neuropsychology test battery that assessed standard domains of cognitive and emotional functioning. Impairment was defined as z-scores = < -1.5 on at least two tests or a z score = < -2.0 on at least one test. Results indicated that over 68% of patients were impaired with nearly a third of the sample showing impairment in verbal learning and memory and approximately one fifth showing impairments in aspects of executive function, processing speed, and visual learning. Ten percent of the patients endorsed symptoms indicative of a clinical level of depression. Medical comorbidities nor depression predicted cognitive impairment. These findings suggest that older adults candidates for HCT are at risk for cognitive impairment prior to transplant and thus cognition should be a consideration when developing treatment plans.

Multiple Myeloma patients eligible for autologous hematopoietic transplantation (AHT) typically receive 3–6 cycles of induction therapy before transplant. The last induction cycle is completed 2–4 weeks prior to mobilization. We evaluated the impact of the time interval between end of induction and AHT on progression-free survival (PFS) and overall survival (OS). A total of 1055 patients who underwent AHT were identified. The median time to transplant (TTT) was 33 days (27–42 quartile range). Patients with less than 33 days of TTT had significantly prolonged PFS (35.6 vs. 32.1 months, p p p

The goal of therapy in AL amyloidosis is to inhibit further production of the amyloidogenic light chains, thereby allowing organ recovery and improving survival. We aimed to assess the impact of depth of hematologic response prior to ASCT on survival. We conducted a retrospective study of 128 newly diagnosed AL amyloidosis patients who received induction prior to ASCT between January 2007 and August 2017 at Mayo Clinic. The overall response rate to induction was 86% (CR 18%, VGPR 31% and PR 38%). With a median follow up of 52 months, the median PFS and OS was 48.5 months and not reached, respectively. Response depth to induction therapy was associated with improved PFS and OS. The median PFS was not reached for patients achieving ≥VGPR prior to ASCT and 34.1 months for patients achieving PR or less (P = 0.0009). The median OS was longer in patients with deeper responses (not reached for ≥VGPR vs. 128 months for PR or less (P = 0.02)). On multivariable analysis, independent predictors of OS were melphalan conditioning dose (RR = 0.42; P = 0.036) and depth of response prior to transplant (RR 0.37; P = 0.0295). Hematologic response prior to transplant predicts improved post transplant outcomes in AL amyloidosis.

We conducted a retrospective study comparing posttransplant outcomes between myeloma patients receiving conditioning melphalan on day-2 vs day-1 for autologous stem cell transplant. Between January 2017 and December 2018, 201 patients received melphalan on day-2 and 166 on day-1 prior to stem cell infusion. Baseline disease and clinical characteristics between the two groups were similar. Although rates of hospitalization were similar between the cohorts, duration of hospital admission was longer for day-1 (median 7 days for day-1 vs 5 days for day-2, p = 0.003). Rates of fever were higher in the day-1 cohort (69% vs 49%, p = 0.0002). Time to platelet and neutrophil engraftment was significantly longer in the day-1 cohort (platelet engraftment median days 17 for day-1 vs 15 for day-2, p

We retrospectively reviewed the impact of impaired renal function (eGFR Stage 1: 100% IRF vs 37% NRF, p

High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations require propylene glycol (PG) as a co-solvent and melphalan has limited solubility and chemical stability after reconstitution, with potential risks for propylene glycol-related complications. Captisol-stabilized propylene glycol-free (PG-free) melphalan has been developed with improved solubility and chemical stability. We compared a cohort of patients with AL amyloidosis receiving PG melphalan (n = 96) to those receiving PG-free melphalan (n = 48) as conditioning for autologous stem cell transplantation. Median time to neutrophil and platelet engraftment was the same; 14 days PG melphalan vs 14 days PG-free melphalan, p = 0.73 and 16 days PG melphalan vs 16 days PG-free melphalan, p = 0.52, respectively. Hospitalization rate was similar in both cohorts, 68% PG melphalan vs 58% PG-free melphalan, p = 0.27. All-cause mortality at 100 days was not statistically significant, 3% PG melphalan vs 2% PG-free melphalan, p > 0.99. Overall response rate (ORR) and rates of complete response (CR) were similar (ORR 93% PG melphalan vs 94% PG-free melphalan, p > 0.99 and CR 39% PG melphalan vs 32% PG-free melphalan, p = 0.46). PG-free melphalan showed a comparable safety and efficacy profile to PG melphalan in patients with AL amyloidosis receiving stem cell transplantation.

Introduction Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65 years of age. The definition of transplant eligible is ill-defined and different centers have different policies to determine which patients are transplant eligible. Some centers have an age cut-off, others use clinical judgment, and some use various frailty scores (a scoring system based on comorbidities and physical and cognitive assessments) aiming to objectively assess transplant eligibility. There are limited data about outcomes in patients ≥ 75 years. Aim To report on outcomes of ASCT in a cohort of patients with MM aged 75 years or older. Methods Retrospective study of all consecutive MM patients aged ≥ 75 years that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Stem cell transplantation at our center is routinely performed as an outpatient, with patients being hospitalized when deemed clinically necessary upon physician review. Results Between October 2005 and March 2020, 46 patients aged 75 years or older, received an ASCT at Mayo Clinic, Rochester. The median hematopoietic stem cell transplantation specific comorbidity index (HCT-CI) was 0 (range 0-6) with 8 patients having HCT-CI of 5 or 6. Median time from diagnosis to ASCT was 6.45 months (IQR 5.2-10.52) and 54% received reduced intensity conditioning with melphalan 140 mg/m2. All patients except one (that was treated with dexamethasone only) received induction with novel agents (listed in table 1) and 6 patients (13%) received doublet induction. All others received triplet induction. 46% of patients completed the ASCT without requiring hospitalization and 54% (n=25) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%) and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients and 16 patients achieving MRD negative sCR. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. Univariable cox regression model that evaluated the effect of gender, high risk cytogenetics, hemoglobin, renal function and melphalan dose did not detect any variable that was predictive of OS or PFS (Table 3). Conclusions ASCT is efficacious and can be safely delivered in the outpatient setting in carefully screened patients aged 75 or above. An arbitrary cutoff for age should not be used to exclude patients from ASCT, rather a careful assessment of "physiological age" including performance status and co-morbidities is required by an experienced treating team. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Cellectar: Other; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; MedImmune: Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Adaptive Biotechnologies: Consultancy. Dispenzieri:Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Dingli:Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy. Kapoor:Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Gertz:Prothena: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Janssen: Other: personal fee; Research to Practice: Other; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Other; Springer Publishing: Patents & Royalties; Celgene: Other; Physicians Education Resource: Other: personal fee; Aurora Bio: Other; Amgen: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Abbvie: Other.

The goal of therapy in AL amyloidosis is to inhibit further production of the amyloidogenic light chains, thereby allowing organ recovery and improving survival. We aimed to assess the impact of depth of hematologic response prior to ASCT on survival. We conducted a retrospective study of 128 newly diagnosed AL amyloidosis patients who received induction prior to ASCT between January 2007 and August 2017 at Mayo Clinic. The overall response rate to induction was 86% (CR 18%, VGPR 31% and PR 38%). With a median follow up of 52 months, the median PFS and OS was 48.5 months and not reached, respectively. Response depth to induction therapy was associated with improved PFS and OS. The median PFS was not reached for patients achieving ≥VGPR prior to ASCT and 34.1 months for patients achieving PR or less (P = 0.0009). The median OS was longer in patients with deeper responses (not reached for ≥VGPR vs. 128 months for PR or less (P = 0.02)). On multivariable analysis, independent predictors of OS were melphalan conditioning dose (RR = 0.42; P = 0.036) and depth of response prior to transplant (RR 0.37; P = 0.0295). Hematologic response prior to transplant predicts improved post transplant outcomes in AL amyloidosis.

We conducted a retrospective study comparing posttransplant outcomes between myeloma patients receiving conditioning melphalan on day-2 vs day-1 for autologous stem cell transplant. Between January 2017 and December 2018, 201 patients received melphalan on day-2 and 166 on day-1 prior to stem cell infusion. Baseline disease and clinical characteristics between the two groups were similar. Although rates of hospitalization were similar between the cohorts, duration of hospital admission was longer for day-1 (median 7 days for day-1 vs 5 days for day-2, p = 0.003). Rates of fever were higher in the day-1 cohort (69% vs 49%, p = 0.0002). Time to platelet and neutrophil engraftment was significantly longer in the day-1 cohort (platelet engraftment median days 17 for day-1 vs 15 for day-2, p 0.0001, neutrophil engraftment median days 16 for day-1 vs 16 for day-2, p = 0.025). Overall response rate was similar between the cohorts (99% for day-1, vs 100% for day-2). Day-2 melphalan infusions should be considered in preference for day-1 protocols, given the clinically significant delay in platelet and neutrophil engraftment and longer duration of hospitalization with day-1 infusions.

Myeloma patients failing to achieve a complete response post autologous stem cell transplantation are heterogeneous, some ultimately achieving deeper responses and prolonged remission, whilst others relapse rapidly with poor outcomes. We evaluated the prognostic impact of the plasma cell proliferative index (PCPI) post-therapy, in 382 patients with myeloma failing to achieve complete response at 100 days post-transplant. Sixty percent (n = 230) of patients had zero clonal or too few clonal plasma cells to accurately assess PCPI (No PCPI). The remaining 40% (n = 152) of patients had PCPI performed with 79% (n = 120) having a low PCPI and 21% (n = 32) having an elevated PCPI. Patients with an elevated PCPI had significantly shorter progression free and overall survival. The median PFS was 8 months for elevated PCPI vs. 19 months for low PCPI vs. 24 months for no PCPI (p

Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment of multiple myeloma (MM). While the procedure is generally safe, toxicities associated with high-dose melphalan conditioning are common and significantly affect patient quality of life. Recently, a propylene glycol-free melphalan formulation (PG-free MEL; Evomela®) was approved by the United States Food and Drug Administration as an ASCT-conditioning regimen for MM. PG-free MEL is more soluble and stable than propylene glycol-solubilized melphalan (PG-solubilized MEL; Alkeran®). As such, there is speculation that it could decrease toxicities and increase the efficacy of ASCT. We compared the outcomes of patients conditioned with PG-free MEL (n = 216) to PG-solubilized MEL (n = 200) at our institution. The baseline characteristics were similar between the two groups. After Day +0, there were no differences in terms of hospitalizations, neutropenic fevers, intravenous granisetron requirement, World Health Organization grade ≥ 2 oral/esophageal mucositis, intravenous fluid requirement, or narcotic requirement. However, PG-free MEL patients had a higher incidence of diarrhea, which was mostly C. difficile-negative (82% vs. 71%, P = 0.015*). Day + 100 hematologic responses and progression-free survival after ASCT were comparable. In summary, we demonstrate that switching to PG-free MEL did not significantly reduce short-term complications of ASCT or improve outcomes in MM.

Hematopoietic cell transplantation is increasingly used in older adults with hematological malignancies. Younger adult patients who undergo HCT have shown to commonly present with cognitive impairment and depression prior to transplant; however, little research has been done to understand the cognitive and emotional functioning of older adults undergoing HCT. This study aimed to investigate the rate of cognitive impairment in a retrospective sample of older adult HCT candidates prior to transplant using a comprehensive battery. Ninety-three patients over the age of 60 completed a neuropsychology test battery that assessed standard domains of cognitive and emotional functioning. Impairment was defined as z-scores =-1.5 on at least two tests or a z score =-2.0 on at least one test. Results indicated that over 68% of patients were impaired with nearly a third of the sample showing impairment in verbal learning and memory and approximately one fifth showing impairments in aspects of executive function, processing speed, and visual learning. Ten percent of the patients endorsed symptoms indicative of a clinical level of depression. Medical comorbidities nor depression predicted cognitive impairment. These findings suggest that older adults candidates for HCT are at risk for cognitive impairment prior to transplant and thus cognition should be a consideration when developing treatment plans.

Use of melphalan in multiple myeloma was observed to have a deleterious effect on stem cell collection in older studies. There is limited data on the impact of melphalan in light chain (AL) amyloidosis, especially in the plerixafor era. We retrospectively evaluated stem cell mobilization in 610 patients with AL amyloidosis, of which 79 had prior exposure to melphalan, 167 to other chemotherapeutics, while 364 had no chemotherapy exposure. Collection of CD34+ stem cells × 106/kg was lower in the melphalan group. Median total yields in the melphalan, non-melphalan, and no chemotherapy groups were 5.5, 7.7, and 7.8, respectively; p 150 mg (median: three cycles) resulting in lower yields. Therefore, duration of melphalan exposure prior to stem cell collection should be limited, ideally, not exceeding more than two cycles of treatment.

This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m2 with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day −22); rituximab 250 mg/m2 with escalating doses of 90Y-Zevalin (day −14); melphalan 100 mg/m2 (days −2,−1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient’s 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20 Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of 90Y-Zevalin with HDM is 18 Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.

Autologous stem cell transplantation (ASCT) is an important treatment modality in light chain (AL) amyloidosis. Use of reduced-dose melphalan conditioning is common, given the associated organ and functional decline. The impact of full-intensity melphalan conditioning (n=314) was compared to reduced-dose conditioning (n=143). Patients in the full-intensity group were younger, with better performance status, fewer involved organs, lower tumor burden and lower Mayo stage. Full-dose conditioning was associated with higher rate of very good partial response or better (79% vs 62%; P