Wagner, Charlotte B

Background: The FDA package inserts for all approved chimeric antigen receptor T-cell (CAR-T) therapies state that patients should universally refrain from driving for 8 weeks following infusion. However, there are no clear data to support this recommendation, particularly in multiple myeloma (MM) which all CAR-T therapies use 4-1BB as opposed to CD28 costimulatory domains. Specifically, no seizures were reported in the KarMMa, KarMMa-3, CARTITUDE-1, or CARTITUDE-4 trials. Because patients typically return to their referring oncologists after Day (D) +28 following CAR-T infusion, an additional month of driving restrictions can create confusion for referring oncologists, impose significant burdens for patients and caregivers, and potentially even affect the choice of MM therapy for patients living in remote areas. Methods: We conducted a two-part study within the US MM Immunotherapy Consortium. Firstly, we analyzed data from commercial idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) recipients (leukapheresis cutoff December 31, 2023) to identify the prevalence of CRS, ICANS, or death between Weeks 5-8 (D+29 to D+56) following CAR-T (Day 0). Patients with index hospital stays lasting over 4 weeks and patients with <8 weeks of post-CAR-T follow-up were excluded. Secondly, we surveyed Consortium members about the prevalence of impaired driving risk (defined as “anything that could impair a patient's ability to drive safely, e.g. seizures, altered mental status, blindness, etc.”) and used 1-5 Likert scales to gauge the perceived importance of driving restrictions (assuming no FDA guidance existed) during Weeks 0-4 vs 5-8. This anonymous IRB-exempted survey was distributed via email to 63 CAR-T-prescribing physicians within the Consortium. Results: Of 553 analyzed patients, 41% (n=224) had received cilta-cel and 59% (n=329) ide-cel. The median age was 64 (IQR 58-70), 42% (n=231) were female, 78% White (n=434), 13% (n=72) Black, and 9% (n=51) Hispanic. ECOG PS at infusion was ≥2 in 11% (n=63) of patients, and 5% (n=28) had had previous CNS co-morbidities such as prior strokes. One patient (0.2%) developed Grade 2 CRS during Weeks 5-8 (onset D+47, resolution one day later); no patients had de novo ICANS after D+28. There were 16 cases of non-ICANS neurotoxicity (including 2 cases of Parkinsonism) diagnosed a median of 24 days after CAR-T (range: 17-147 days), of which 3 cases (all non-Parkinsonian) were first diagnosed during Weeks 5-8. There were 10 deaths (2%) during Weeks 5-8, one due to infection and the remainder from progressive MM. The survey was completed by 45 oncologists (71% response rate), 41 of whom had managed both >5 ide-cel and >5 cilta-cel recipients. Regarding impaired driving during Weeks 0-4, 20% of physicians felt this was never a risk, 36% a risk for 1-2% of patients, 29% a risk for 3-10% of patients, and 16% a risk for >10% of patients. The distribution was significantly different (p < 0.01) for Weeks 5-8: 49% never a risk, 36% a risk for 1-2% of patients, 16% a risk for 3-10% of patients, while no respondents felt this remained a risk for >10% of patients. For Weeks 0-4, 73% agreed that patients should be advised not to drive while 9% disagreed. In contrast, for Weeks 5-8, 14% of physicians agreed with driving restrictions while 78% disagreed (p < 0.01 compared to Weeks 0-4). Discussion: Our two-part study demonstrates that driving restrictions following Week 4 after CAR-T therapy in MM may not be required. The incidence of de novo CRS or any-type neurotoxicity being diagnosed during Weeks 5-8 was <1%, and - if such toxicities developed - patients and physicians could be expected to set appropriate restrictions at that juncture. While 73% of CAR-T-prescribing oncologists agreed that patients should refrain from driving during Weeks 0-4, 78% disagreed with this recommendation during Weeks 5-8. These findings complement other real-world studies (Wesson, Dima, et al, TCT 2024; Ahmed et al, Blood Advances 2024) reporting the rarity of CRS and ICANS after the first month in both MM and lymphoma. Our study is limited by a lack of patient-reported data, which was done intentionally to avoid asking patients about activities undertaken against medical advice. Nevertheless, we believe that narrowing universal driving restrictions to Weeks 0-4 following CAR-T therapy would constitute an evidence-based modification to the package inserts for ide-cel and cilta-cel.

Introduction. Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), two anti-B-cell maturation antigen (BCMA) CAR T therapies, have demonstrated remarkable responses and improved survival among patients with relapsed/refractory multiple myeloma (RRMM) in the clinical trials and standard of care (SOC) setting. Here, we compare safety, efficacy, and survival for patients treated with SOC ide-cel and cilta-cel. Methods. Data were from a retrospective chart review of RRMM patients leukapheresed by 12/31/2022 with the intent to receive SOC ide- or cilta-cel at 19 institutions in the US Multiple Myeloma Immunotherapy Consortium. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type (cilta- vs. ide-cel), balancing on age, sex, race and ethnicity, performance status, extramedullary disease, high-risk cytogenetics, prior BCMA therapy, bone marrow plasma cells, penta-refractory status, lymphodepleting chemotherapy, baseline ferritin, low cell dose, and bridging therapy response. Logistic regression and Cox proportional hazard models were used to examine the association of treatment type with safety, efficacy, and survival accordingly, while adjusting for IPTW weights. We employed propensity score matching utilizing the same covariates to identify the association of treatment type with progression-free survival (PFS) within relevant patient sub-groups. Results. A total of 641 patients were leukapheresed by 12/31/2022 with ide-cel (n=386) and cilta-cel (n=255). 586 patients were infused (n=350 for ide-cel; n=236 for cilta-cel) with a median follow-up of 13.0 and 12.6 months, respectively. After IPTW, patient characteristics were well-balanced. Patients treated with cilta-cel were more likely to have grade ≥ 3 cytokine release syndrome (CRS) (OR=5.52, 95% CI=1.76-17.30, p=0.004), infections (OR=2.07, 95% CI=1.44-2.97, p<0.001), and delayed neurotoxicity (NT) (OR=20.97, 95% CI=4.75-92.42, p<0.001) compared to patients treated with ide-cel. In the cilta-cel cohort, 24 patients (10%) experienced delayed NT compared to 2 patients (1%) in the ide-cel cohort. Although not statistically significant, patients treated with cilta-cel were more likely to have any second primary malignancies (SPMs) (OR=1.87, 95% CI=0.94-3.71, p=0.08) and any SPMs excluding non-melanoma skin cancers (OR=1.78, 95% CI=0.78-4.10, p=0.2) but no association was observed for odds of hematologic SPMs (OR=0.98, 95% CI=0.26-3.61). No association was observed for therapy type with any or severe immune effector cell-associated neurotoxicity syndrome, any CRS, severe cytopenias, and non-relapse mortality. Compared to ide-cel, cilta-cel was associated with better treatment responses of ≥ complete response (OR=2.38, 95% CI=1.61-3.51, p<0.001) and ≥ partial response (OR=1.74, 95% CI=0.99-3.05, p=0.06). Patients treated with cilta-cel had a longer PFS and overall survival (OS) than ide-cel (HR=0.47, 95% CI=0.35-0.62, p<0.001 and HR=0.63, 95% CI=0.42-0.93, p=0.02, respectively), and these findings were similar in the intention to treat cohort (PFS: HR=0.44, 95% CI=0.34-0.55, p<0.001; OS: HR=0.55, 95% CI=0.41-0.73, p<0.001, respectively). We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time-period as FDA approval for cilta-cel (≥ March 2022), restricting to patients with data on all covariates, and restricting to sites that contributed data for both products. In a propensity matched population, (n=380; n=190 for cilta-cel and n=190 for ide-cel), patients treated with cilta-cel had superior PFS compared to those treated with ide-cel in most subgroups with respect to age and disease characteristics including extramedullary disease, high-risk cytogenetics, and elevated baseline ferritin (p<0.05). Conclusion. Our results suggest superior efficacy of cilta-cel with a higher incidence of certain toxicities compared to ide-cel in the SOC setting. This study provides valuable information for patient counseling and guiding the selection of CAR T-cell therapy for specific patient populations. Further validation through similar large-scale real-world experiences or prospective studies is needed to confirm our results and enhance applicability in the clinical setting. *DH, LP, & DD are co-first authors * YL, KP, & SS are co-last authors

Introduction: Anti-BCMA CAR-T therapies like idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized RRMM treatment. However, the 6-8-week manufacturing period often leads to disease progression and/or death in up to 25% of patients (pts), necessitating effective bridging strategies. Talquetamab (talq), a bispecific antibody targeting GPRC5D, is approved for RRMM pts with four prior lines of therapy and offers rapid disease debulking without impacting BCMA. This study assesses the safety and efficacy of a short course of talq as a bridging therapy for pts receiving cilta-cel or ide-cel. Methods: This multicenter retrospective study involved 14 US academic medical centers within the US Multiple Myeloma Immunotherapy Consortium. We included pts with RRMM who underwent leukapheresis and received talq bridging therapy with the intent to proceed to commercial cilta-cel or ide-cel. We assessed the safety, feasibility, and efficacy of talq bridging therapy. Safety outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), talq-related unique toxicities, and delayed neurotoxicity (NT). Efficacy outcomes included response rates to talq and CAR-T therapies. Results: Between June 2023 and May 2024, 77 pts received talq bridging therapy after apheresis with the intention to proceed to CAR-T. The median age was 66 years (range, 58-73); 14% were Black and 10% Hispanic. Poor prognostic features, including high-risk cytogenetics, were present in 45%, extramedullary disease (EMD) in 43%, and 72.7% were triple-class refractory. The median number of prior lines of therapy was 5 (range 3-11) and 10 pts (13%) had prior BCMA targeted therapy. Out of 77 pts, 10 pts were pending CAR-T infusion at the time of last follow up; 6 pts could not receive CAR-T infusion due to manufacturing failures. Of the remaining 61 patients who underwent successful CAR-T manufacturing, 58 (95%) pts were successfully infused with CAR-T therapy following talq bridging. Three (5%) pts died due to disease progression prior to CAR-T infusion. Talq was given 0.8 mg/kg biweekly in 59 (76%) pts and the median time on talq was 22 days (IQR: 10-41 days). Following talq bridging, none of the pts had grade >=3 CRS and 2 (2.5%) had grade 3 ICANS. Skin toxicities occurred in 32 (41%), nail toxicities in 19 (25%), and oral toxicities in 43 (56%) pts mainly grade 1. Most oral, skin, and taste changes resolved at the last follow-up (60%). Response to talq was evaluable in 72 out of 77 patients. An overall response was noted in 45/72 (62%) pts including unconfirmed CR in 14, VGPR in 10 and PR in 21 pts. There was no association of AEs and response to talq with high-risk cytogenetics, EMD and high baseline ferritin levels. Out of the 58 patients who went on to receive CAR-T therapy following talq bridging (45 cilta-cel and 13 ide-cel), 38 (65%) experienced CRS, with grade 3 CRS noted in 2 (3%) pts. ICANS occurred in 5 (8.6%) pts, with 1 (1.7%) grade 3 ICANS. Only 1 pt had delayed NT (facial nerve palsy) at the last follow up. No treatment related deaths were observed. Of these 58 pts, response was evaluable in 40 pts and a response at day +30 was noted in 39/40 (97.5%) pts (14 in CR, 10 in VGPR, 15 in PR). The median follow-up from CAR-T was 61 days (28-113). For the 58 pts who received CAR-T, the median time from the last talq dose to CAR-T infusion was 25 days (IQR: 19-36), and to lymphodepletion was 24 days (IQR: 18-33). There was no difference in the CAR-T related AEs by the duration of Talq washout (>4 weeks vs. =< 4 weeks). Conclusions: Talquetamab is an excellent bridging option before BCMA-targeted CAR-T therapy, showing high response rates even with short-term use and enabling most pts to receive CAR-T. Most oral, skin, and taste changes resolved post CAR-T. These findings underscore the effectiveness of a short course of talq bridging to maintain disease control and improve outcomes post CAR-T. Updated data with longer follow-up will be presented at the meeting.

Abstract Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell–associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen–targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.

Abstract In a retrospective analysis at 11 US medical centers, bridging therapy (BT) impact after receiving idecabtagene vicleucel was assessed in 214 patients. 79% received BT, including 12% Selinexor-containing, 45% alkylator-based, 15% proteasome inhibitor combinations, and 18% immunomodulatory drugs +/- monoclonal antibody combinations (IMiD +/- mAb combos). BT recipients had worse performance status, higher stage disease, ferritin and CRP pre-infusion. The overall response rate to BT was 12%, with no difference among BT subgroups. Safety profiles were similar, but Selinexor had a higher grade ≥2 ICANS incidence. Median progression-free survival (PFS) was 6.7 months in BT vs. 11.5 months in no-BT (p=0.007). Median PFS was longest with IMiD +/- mAb combos (12 months), comparable to no-BT, and significantly longer than other BT subgroups (p=0.01). Alkylator-based BT had inferior PFS compared to IMiD +/- mAb combos (p=0.03). Median overall survival (OS) for the BT was 13.8 months vs. not reached in no-BT (p=0.002). Alkylator-based BT had shorter OS compared to others (11.97 months vs. NR; p=0.001). Stepwise Cox regression showed alkylator-based BT and response

Introduction: Lymphodepletion (LD) chemotherapy is critical for the efficacy of CAR-T therapy by eradicating immunosuppressive cells, inducing costimulatory molecules, and promoting expansion and persistence of CAR-T cells. It also can contribute to an increased risk of infections, cytopenia, and other toxicities. We evaluated the utilization of varying LD regimens used in standard-of-care (SOC) autologous B-cell maturation antigen-directed (BCMA) CAR-T therapy with ide-cel or cilta-cel for relapsed/refractory multiple myeloma (RRMM) and the effect on outcomes and toxicity. Methods: Data were retrospectively collected from patients with RRMM who underwent LD and CAR-T cell infusion by December 31, 2022, from 13 US academic institutions with SOC ide-cel or cilta-cel. Response rates and other categorical variables, specifically LD regimen, were tested for association using Wilcoxon rank-sum (or Kruskal-Wallis for three or more groups) or Fisher's exact tests, respectively. Results: A total of 523 patients were infused at the time of data cut-off with 489 patients evaluable for safety and survival analyses; 368 (75%) were infused with ide-cel and 121 (25%) with cilta-cel. The median age was 65 years old (range 30-90) with 206 females (42%) and 283 males (58%), and 13% with ECOG performance status ≥ 2 at time of LD. Fludarabine and cyclophosphamide (Flu/Cy) LD was used in 422 patients while 67 patients received other LD regimens including bendamustine-based (n = 35, 52%), cladribine-based (n = 25, 37%) or cyclophosphamide alone (n = 7, 10%). The primary reason for use of Flu/Cy LD was institutional guidance or SOC in 378 patients (90%), while the primary reason for use of other LD regimens was due to the fludarabine shortage in 65 patients (97%) with 3% citing physician's choice or institutional guidance. No significant difference was identified among response outcomes, with those receiving Flu/Cy LD achieving an ORR of 84% compared to 81% with other LD regimens (p = 0.59) and no difference observed in rates of ≥ VGPR (66% Flu/Cy LD vs 60% other LD; p = 0.48). Of those evaluable for MRD at 1 and 3 months, the MRD negative rate at 10 -6 for those with Flu/Cy LD was 77% (n= 137) and 77% (n=113) and with other LD regimens was 66% (n=35) and 79% (n=28), respectively. At a median follow-up of 9.7 months, no statistically significant difference was noted in median progression free survival (mPFS) with Flu/Cy vs other LD regimens (9.3 mos vs NR) or overall survival (OS) (19.4 mos vs NR). When stratified by type of CAR-T therapy, treatment with bendamustine-based LD was associated with an inferior mPFS compared to those receiving Flu/Cy LD in patients treated with ide-cel (3.8 vs 8.5 mos; p=0.0056), though not by multivariate analysis. Univariate analysis of patients treated with ide-cel between Flu/Cy and bendamustine LD did not reveal any significant differences in age, gender, ECOG, R-ISS stage, extramedullary disease, high-risk cytogenetics or renal dysfunction (Cr < 45 ml/min). LD regimen was not a predictor for PFS on multivariable analyses amongst patients treated with ide-cel, while ECOG ≥ 3 (hazard ratio [HR]= 4.44, 95% confidence interval [CI]= 1.40, 14.08) and t(4,14) (HR= 2.02, 95% CI=1.14, 3.59) were associated with worse PFS. No difference in mPFS by LD regimen was observed in patients receiving cilta-cel, which was a smaller cohort (mPFS: Flu/Cy 11.7 mos, bendamustine-based NR, cladribine-based NR, cyclophosphamide NR). Rates of all grade CRS (81% vs 70%), Grade ≥ 3 CRS (3% vs 3%), all grade ICANS (19% vs 12%, and Grade ≥ 3 ICANS (4% vs 2%) were similar among those receiving Flu/Cy or other LD regimens, respectively. Patients receiving Flu/Cy LD were less likely to have any grade cytopenia at 1 month (33% vs 55%, p < 0.001) and 3 months (52% vs 69%, p < 0.001), with no observed difference in infection rate. Conclusions: The fludarabine shortage experienced in the US in late 2022 necessitated the use of alternative LD regimens with BCMA-directed CAR-T therapy with most centers relying on bendamustine- or cladribine-based regimens. Use of bendamustine-based LD was associated with inferior PFS in patients receiving ide-cel on univariate analysis, but not on multivariate analysis after adjusting for other prognostic factors. In summary, there is no clear difference in efficacy or safety between Flu/Cy and non-Flu/Cy LD in patients receiving BCMA-directed CAR-T therapy. *Authors contributed equally

Abstract Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

8013 Background: Ide-cel is an FDA-approved treatment for RRMM patients (pts). However, there is limited data on how BT for disease control during its manufacturing process affects clinical outcomes. Methods: Eleven US academic centers contributed data to this analysis without involvement from the manufacturer. By 5/1/2022, 235 pts had undergone leukapheresis, with 214 infused with a median follow up of 9 months (mos). BT was given between leukapheresis and CAR-T infusion. Results: In this analysis, 79% of pts (n = 170) received BT, which included alkylator-based in 35.5%, steroid and/or IMiD/Ab combos (IMiD combos) in 14%, PI combinations (PI combos) in 12%, and selinexor in 10%. BT recipients had higher ECOG PS 2-4, R-ISS 2-3, ferritin, and CRP before lymphodepleting (LD) chemo, however, no difference among BT subgroups. No difference in prior lines of therapy or penta-refractory between BT and No BT (NBT) groups or BT subgroups. Median cycle of the BT was 1 (1-7), with overall response rate (ORR) of 12%, with no difference among BT subgroups. Incidence and severity of CRS and ICANs were comparable in BT and NBT. However, pts who received BT had a longer median hospital stay compared to NBT, particularly in the alkylator/selinexor subgroups. There were no significant difference in cytopenias at day 90 post CAR-T between the BT and NBT or BT subgroups. For the 73% (n = 157) evaluable for day 90 response, there was no difference in the complete or ORR between the BT and NBT groups (41% vs. 52%; p = .2 and 84% vs. 87.5%, p = .8, respectively). Median PFS was worse at 8.1 mos in BT vs 11.5 mos in NBT (p = .03). Among BT subgroups, PFS was the longest with IMiD combos with median PFS not reached (NR), comparable to NBT, and was significantly longer than all other BT subgroups (p = 0.01). The median OS was 13.8 mos with BT and NR in NBT (p = .002). In BT subgroup analysis, alkylators had a shorter OS, although, this was not significant (p = .06). There was no significant difference in PFS and OS in relationship to response to BT (p = .6 and p = .9, respectively). Conclusions: Pts without BT had longer PFS and OS post ide-cel, likely reflective of less aggressive disease. Those who received BT with steroid/IMiD and Ab combos had similar PFS as NBT. However, BT choice is complicated by disease severity and should be evaluated per patient circumstances. [Table: see text]

7514 Background: The AETHERA trial demonstrated improvement in PFS with 16 cycles of brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in BV-naive patients with high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL). However, in real world, patients are rarely able to complete all 16 cycles of BV at full dose. We performed a multicenter retrospective study to assess the impact of cumulative dose on toxicity and 2-year PFS. Methods: Patients from 11 institutions across the US who had received at least one cycle of BV maintenance after ASCT for r/r cHL with one of these features were included: primary refractory disease (PRD), extra-nodal disease (END), or relapse < 12 months of diagnosis (RL<12). PFS was compared between the three cohorts based on a total cumulative dose of 28.8 mg/kg (1.8 mg/kg x 16 cycles): C1, those that received >75% (21.7 to 28.8 mg/kg) cumulative dose of BV, C2, those that received between 51% -75% (14.5 to 21.6 mg/kg) dose and C3, those that received ≤ 50% (≤ 14.4 mg/kg) dose. Results: Between July 2015-June 2019, 100 patients with a median age of 34 years (19-70) underwent ASCT for r/r cHL. At relapse, 44% had PRD, 47% had RL<12, 39% had END and 45% had received BV as initial (1%) or salvage (44%) therapy. 71% had CR before ASCT and 23% received >1 line of salvage (>1 SLT). There was no difference in baseline characteristics between the cohorts. Thirty-six patients were in C1, 27 in C2, and 37 in C3. Only 14% of patients received full cumulative dose of BV. The median number of cycles completed was 12. Fifty-seven patients discontinued early: 39 for toxicity, 7 for progression, 5 for patient preference, 2 for cost and 4 for other reasons. Six of the patients who stopped early for progression were in C3. Grade ≥3 adverse events for neuropathy, neutropenia, and infections were 16%, 7%, and 5% respectively. There was no difference in severity of neuropathy in patients who had received BV prior to ASCT (p=.37). The median follow up was 3.37 years (.4–6.35). The 2-year PFS was 85% for all subjects, 94% for C1, 84% for C2, and 72% for C3 (p=.079) (Table). Patients in C3 had worse PFS compared to C1 (p=.035); this difference remained significant after adjusting for five other factors. There was no difference in PFS between C1 and C2 (p=.29). Conclusions: The majority of patients discontinued BV maintenance early due to toxicity. 2-year PFS was robust regardless of cumulative dose of BV. We conclude that total cumulative dose of 28.8 mg/kg of BV maintenance is not necessary and 51%-75% of total BV dose may still attain a similar PFS advantage. [Table: see text]