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  • American Society of Clinical Oncology (ASCO)  (7)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 8049-8049
    Abstract: 8049 Background: Teclistamab (Tec) is the first CD3 x BCMA bispecific antibody (BsAb) receiving accelerated FDA approval for treatment of relapsed or refractory multiple myeloma (RRMM) in patients who have received ≥4 prior lines of therapy, including a PI, IMiD and an anti-CD38 monoclonal antibody. The approval was based on the results of the MajesTec-1 study (Usmani S et al Lancet 2021, Moreau P et al NEJM 2022), demonstrating a 63% overall response rate in a heavily pretreated RRMM population. Patients with prior exposure to anti-BCMA therapies, such as BCMA targeted ADCs, CAR T-cell products and BsAbs were excluded from this study. Herein, we present our institutional experience with commercial Tec for RRMM including patients with prior BCMA and GPRC5D directed therapies. Methods: We have performed an IRB-approved, retrospective analysis of clinical outcomes of all patients who have received commercial Tec at MSKCC since its approval on 10/26/2022 using the PCD research database. Descriptive analyses were performed for baseline characteristics. The IMWG criteria (Kumar S et al, Lancet Oncol 2016) were used to assess response and define prior therapy refractoriness. Immune profile was assessed via high-dimensional flow cytometry using lineage, exhaustion, and activation markers. Serum soluble BCMA levels were assessed using an immunoassay. Results: As of 2/4/2023, 24 patients have received commercial Tec and 15 are response evaluable with ≥1 month of clinical follow-up. Median age was 66 (51-80), prior lines of therapy was 7 (4-13), time from diagnosis was 7 years (1.5-16), 53% had high-risk cytogenetics, and 40% had EMD. All patients were triple class refractory and 80% were penta-drug refractory. Ten had prior anti-BCMA therapy (7 Belamaf, 8 BCMA CART, 1 BCMA BsAb, 5 with ≥2 anti-BCMA therapies). With a median follow-up time of 1.3 months, the median time to response was 16 days. ORR was 60% (9/15) in all patients and 50% (5/10) in the prior anti-BCMA therapy group. Pts with ≥2 anti-BCMA therapies had a 40% (2/5) response rate to Tec. Clinical benefit rate (CBR) in all patients was 73% (11/15). None of the responders have progressed at this short follow-up time. Cytokine release syndrome was observed in 7/15 patients (41%) during step-up dosing (5/7 with g1 and 2/7 with g2 CRS) and CBR was 100% in patients with CRS (71% ORR). Other notable toxicities include 2 patients with grade 2 neurotoxicity that improved with therapy discontinuation. Conclusions: To our knowledge, this is the first report of commercial Tec in RRMM. Tec remains effective in RRMM despite prior exposure to anti-BCMA therapies, though exposure to multiple prior anti-BCMA therapies may be predictive of diminished efficacy. Clinical data on additional patients will be presented at the meeting. Ongoing translational investigations on soluble BCMA levels and patient-specific immune phenotype will also be presented at the meeting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 28 ( 2021-10-01), p. 3109-3117
    Abstract: We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550 ). METHODS Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m 2 IV, days 1 and 8), vinorelbine (20 mg/m 2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m 2 , days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 8023-8023
    Abstract: 8023 Background: Plinabulin is a selective immunomodulating microtubule-binding agent, which prevents chemotherapy induced neutropenia (CIN) via a mechanism of action different from that of G-CSF analogues. It has been studied for CIN and anti-solid tumor activity in phase 3 trials. To decrease the period of myelosuppression and obligate neutropenia after high dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for patients with multiple myeloma, we studied the addition of plinabulin to standard growth factors. Methods: To achieve the primary objective of reducing the duration of absolute neutropenia post AHCT, 40mg of intravenous plinabulin was given 1-3 hours after stem cell infusion (Day 0) with pegfilgrastim on Day +1 in this pilot trial (NCT05130827). Secondary objectives include the safety, tolerability, and toxicity profile of plinabulin in combination with pegfilgrastim, neutrophil and platelet engraftment rate, disease response, progression free and overall survival, patient reported outcome (PRO) assessment of symptom burden, and plinabulin pharmacokinetic profiling. Exploratory objectives include transfusion requirements, phenotypic characterization of neutrophil population through day 30, and analysis of cytokine levels early post AHCT. Results: Between January 2022 and February 2023, 15 patients with median age of 64 (range 54-74) and 33% female received plinabulin after melphalan 140 (n = 4) or 200mg/m2 (n = 11). Median CD34+ cells/kg infused was 4.12 x 10^6 (range 2.18 – 7.85). Half of the patients had hypertension immediately after the plinabulin infusion, which is a known toxicity and resolved within a few hours. Median WBC on Day 0, 1, and 2 was 7.67(3.6 – 11.5), 5.2 (3.2 – 13.6), and 17.1 (5.1-59.1), respectively. Of the 14 patients who have engrafted to date, median time to ANC 〉 0.5 x 10^9 cell/L was 11 days (range 9-16) with median days from AHCT to ANC 〈 0.5 of 5 days (range 5-6). The median number of days of ANC 〈 0.1 and 〈 0.5 were 2 (range 1-5) and 5 days (range 4-9), respectively. For the 7 patients who had a fever, the median time to fever was 8 days from AHCT (range 8-12), and all except one were peri-engraftment. Median length of stay was 17 days (range 15-21). Median pRBC and platelet transfusions were 0 (range 0-3) and 3 (range 0-11), respectively. Conclusions: Plinabulin appears well tolerated without additional major toxicities post AHCT and provided a high WBC on Day +2 and decreased rate of neutropenic fever. Plinabulin PK, quality of life data, and PROs will be presented. Adjusting the schedule of plinabulin to later post AHCT pre engraftment may further shorten the duration of neutropenia using this novel mechanism of action. Clinical trial information: NCT05130827 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 8045-8045
    Abstract: 8045 Background: The incidence of multiple myeloma (MM) is two to threefold higher in African Americans (AAs) compared to whites when adjusted for socioeconomics, age, and sex. However, there is limited information on whether racial background affects the risk of progression from smoldering MM (SMM) to MM. Methods: Patients with SMM presenting to Memorial Sloan Kettering Cancer Center between the years 2000 and 2019 and who identified as either AA or white were included in the study. Baseline characteristics were collected at the time of diagnosis including laboratory, imaging, and pathology reports. Differences in distributions of continuous and discrete characteristics were assessed by Kruskal-Wallis and chi-square tests. Time to progression (TTP) was assessed using the Kaplan-Meier method with log-rank test for comparisons. Univariate and multivariate Cox proportional hazard models were used to estimate effects of risk factors on TTP with hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 576 patients were included (70 were AA, 12%). Median follow-up time was 3 years in AAs and 4 years in whites. Differences in baseline characteristics between AAs and whites included median age (60 years in AAs vs 64 years in whites, p = 0.01), median hemoglobin level (12.3g/dL in AA vs 12.8g/dL in whites, p = 0.02), and immunoparesis including 1 or 2 uninvolved immunoglobulins (31% and 10% in AAs vs 56% and 27% in whites, p = 0.002). There was no difference in bone marrow plasma cells, M-spike, free light chain ratio, or Mayo-2018 SMM risk score. AA race was associated with a significantly decreased risk of progression in the univariate model (HR 0.57, CI 0.34-0.94). In the multivariate model adjusting for age, sex, and variables associated with an increased risk of progression in the univariate model (bone marrow plasma cells, M-spike, free light chain ratio, immunoparesis and low albumin), AA race remained associated with a decreased risk of progression (HR 0.39, CI 0.16-0.95). Overall, AA patients with SMM had a significantly (p = 0.027) longer median TTP (9.7 vs 6.2 years), and a lower 2-year (12.6% vs 20.1%) and 5-year (34% vs 44.6%) progression rate than whites. Because AA patients were younger at diagnosis, we stratified patients by age group, 〈 65 vs ≥65 years. In patients 〈 65 years, there was no difference in progression rate. In patients aged ≥65 years, AA patients continued to have a longer TTP than whites (9.8 vs 5.2 years, p = 0.02). Conclusions: In our retrospective single institution experience, AA patients with SMM had a lower risk of progression to MM compared to whites. Both groups had similar Mayo-2018 risk scores, however, AA patients had a lower degree of immunoparesis at baseline. Future studies are needed to better understand if these differences are explained by differences in disease biology including genomic mechanisms, immune microenvironment, and systemic immune response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e20005-e20005
    Abstract: e20005 Background: DARA has been FDA approved for newly diagnosed multiple myeloma (NDMM) in combination with lenalidomide/dexamethasone (Rd), bortezomib/melphalan/dex, and bortezomib/thalidomide/dex since 2018. With the increase use of DARA combinations in NDMM, understanding the role of DARA retreatment at relapse needs to be examined in clinical practice. Herein, we describe a single institution experience of the efficacy of DARA-based retreatment as second line of therapy (LOT2) for patients (pts) who received DARA-based induction compared to DARA-free induction regimens. Methods: Thirty-three pts treated with DARA-based LOT2 at MSK from 1/2015 to 9/2021 were included in this retrospective analysis. Primary endpoint was overall response rate (ORR; ≥PR by IMWG criteria). Discrete patient characteristics were summarized by frequency (percentage) and continuous characteristics were summarized by median (IQR). Progression free survival (PFS) was evaluated by Kaplan-Meier method. Results: Two cohorts were identified based on prior DARA exposure: cohort 1 (N=6) received DARA-based induction without meeting DARA-refractory criteria and cohort 2 (N=27) had carfilzomib and Rd (KRd) induction (Table). Median follow-up was 13.8 and 14.5 months for cohorts 1 and 2, respectively. In cohort 1, 5 pts received DARA-KRd and 1 had DRd as first line therapy (LOT1). Median time between last dose of DARA in LOT1 and first dose of DARA in LOT2 was 17.5 months (IQR 12.1-19.8). ORR were 83% and 79% for cohorts 1 and 2, respectively. In cohort 1, ORR comprised of 1 sCR, 1 VGPR, and 3 PR. For cohort 2, there were 5 sCR/CR, 7 VGPR, and 9 PR. Median PFS was not reached in cohort 1 and 16.2 months in cohort 2. Conclusions: In a cohort of pts retreated with DARA after DARA-based induction, our findings suggest that DARA-exposed MM pts may derive benefit from DARA retreatment in subsequent lines of therapy similarly to pts who were DARA-naïve prior to DARA-based LOT2. Longer follow-up is needed to assess survival outcomes. In addition, larger confirmatory studies are warranted to further characterize response characteristics of DARA combinations in LOT2, especially as DARA-based therapy is increasingly used in treating NDMM. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 8047-8047
    Abstract: 8047 Background: In 2014, the definition of multiple myeloma was updated to include serum free light chain (FLC) ratio ≥100 as a myeloma defining biomarker, based on retrospective data indicating a 2-year progression rate of 80% and a median time to progression (TTP) of 12 months associated with this marker. However, two recent studies have reported lower 2-year progression rates, 30-44%, and longer median TTP of 40 months in patients with FLC ratio ≥100. Because of the disparity in risk prediction by FLC ratio across studies, we were motivated to assess the risk of progression in patients with SMM and a FLC ratio ≥100. Methods: We performed a retrospective analysis of patients diagnosed with SMM at Memorial Sloan Kettering Cancer Center between January 2000 and December 2017. Diagnosis of SMM and progression to MM was defined according to the International Myeloma Working Group (IMWG) criteria at the time of diagnosis. Kaplan-Meier method was used to assess TTP and generate survival curves, with log-rank test for comparison between groups. Results: A total of 438 patients were included in the study, with a median follow-up time of 52 months. While all patients with a FLC ratio ≥100 (n = 66) had elevated involved FLC levels, 35 (53%) had an involved FLC concentration 〉 100 mg/L. Per current diagnostic criteria, we only included patients with an involved FLC concentration 〉 100 mg/L in the FLC ratio ≥100 group, and found a median TTP of 31 months (95% confidence interval [CI] 16-59 months) and a 2-year progression rate of 49% (CI 28-63%). In a sensitivity analysis including all 66 cases with FLC ratio ≥100 (independent of involved FLC concentration), we found the median TTP to be 41 months (CI 30-72 months), compared to 101 months for those with a FLC ratio 〈 100 (CI 78-127 months; p 〈 0.0001). The risk of progression within 2 years was 35% (CI 22-46%) compared to 18% (CI 14-23%; p 〈 0.0001). Of note, 22 patients with a FLC ratio ≥100 were monitored expectantly for 〉 4 years, among whom 12 patients had an involved FLC level 〉 100 mg/L. Ten patients (7 with involved FLC level 〉 100 mg/L) were followed over a period ranging from 4 to 8.5 years before eventually progressing, and 12 patients (5 with involved FLC level 〉 100 mg/L) were followed between 4 and 8 years and did not progress during the study period. Conclusions: While FLC ratio ≥100 is associated with a high risk of progression in patients with SMM, it does not infer an imminent risk of progression, defined by the IMWG as median TTP of 12 months and 2-year progression rate of at least 80%. On the contrary, select patients with FLC ratio ≥100 can be followed for many years without progressing and some may never progress despite long-term follow-up. These findings suggest that in patients where FLC ratio ≥100 is the only myeloma-defining event, other high-risk features as well as the evolution of FLCs over time should be considered in the decision to start a patient on treatment.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 8051-8051
    Abstract: 8051 Background: Patients with high risk smoldering multiple myeloma (HR-SMM) have an increased risk of progression to multiple myeloma (MM)- median time 〈 2 years. The standard management of these patients currently is close clinical monitoring; however, randomized trials show longer progression-free and overall survival in in HR-SMM patients treated with the oral immunomodulatory drug lenalidomide. We report the use ixazomib, the first oral proteasome inhibitor, in combination with dexamethasone in the setting of HR-SMM. Because proteasome inhibitors can provide deep clinical responses in patients with MM, we set the pre-specified threshold for efficacy high (overall response rate of ≥75%). Methods: In this single arm pilot trial of ixazomib/dexamethasone, patients received 12 4-week cycles of ixazomib/dexamethasone followed by ixazomib maintenance for 24 cycles. The primary endpoint is best overall response after 12 cycles and second objectives include duration of response, safety, and progression free survival. Results: 14 patients with HR-SMM were enrolled between 06/2016 and 03/2018. The median age is 65 years and 10 (71%) of patients were male. 11 (79%) patients were high-risk by the PETHEMA criteria, 2 (14%) by the Mayo Clinic criteria and 1 (7%) by both. At data cut-off (02/07/2019), patients completed a median of 17 cycles and 10 (71%) are continuing treatment. 4 patients have stopped treatment (2 patients for raise in serum markers without progression to MM, and 1 each for toxicities, and co-morbidities unrelated to treatment). 9 (64%) achieved an objective response (8 PR, and 1 VGPR) and no patient has progressed to MM. Non-heme adverse events included 3 grade 1 GI events, 2 grade 3 lung infection, 1 grade 2 acute kidney injury, and 1 had grade 1 fatigue that was possibly related to treatment. Conclusions: Ixazomib/dexamethasone appears well tolerated with high overall response (9/14; 64%) in patients with HR-SMM. Although the trial does not meet our pre-specified threshold for efficacy (i.e. best overall response rate of 75%), with a median follow-up of 17 months, no patient progressed to MM and only 2 patients had serologic progression. These results support further evaluation of ixazomib/dexamethasone alone and in combination with other agents as treatment for patients with HR-SMM. Clinical trial information: NCT02697383.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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