Demographics and Outcomes of Multiple Myeloma Patients Undergoing Modern Modality Treatments Proceeding to ASCT: A Retrospective Study

Abstract Introduction: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. With the advent of novel therapies for multiple myeloma and emerging data from randomized trials, there has been a substantial improvement and favorable outcomes in survival. Here, we report demographics and outcomes in a cohort of patients who underwent Autologous Stem Cell Transplant (ASCT) over the past year. Methods: In this retrospective, cohort study, we assessed all MM patients who received ASCT from January 1, 2020, to January 15, 2021, at Cleveland Clinic, and followed until July 31, 2021. Baseline demographics, ECOG performance status, ISS stage, cytogenetic risk category, therapy received before ASCT, maintenance therapy, time to first relapse/progression, time to next treatment (TTNT; 2nd line of treatment onwards) with treatment response (defined per IMWG response criteria) before and after ASCT were obtained by review of electronic medical records. All patients received HDCT Melphalan 140 mg/m2 or 200 mg/m2 prior to ASCT. Continuous variables were presented as median and interquartile range, while categorical variables were presented as numbers and percentages. Categorical variables were compared using the chi-square test. Results: Of 81 MM patients who underwent ASCT, 59% were males, 84% were white, with a median age of 62 (IQR: 57-67) at the time of diagnosis. 42 (52%) and 24 (30%) patients belonged to the standard and high-risk category. Amongst high-risk cytogenetic abnormalities, +1q was the most common (72%) followed by del(17p) (28%). Baseline characteristics of patients are included in Table 1.1. Lenalidomide, bortezomib, and dexamethasone (VRd) regimen was the most common (75%) first-line induction regimen used, followed by Daratumumab-based regimens (20%). 10 (12%) patients required second-line treatment, and 6 (7%) patients required more than 2 lines of treatments prior to transplant. The median time to transplant was 6.5 months. The overall response rate (ORR) prior to transplant was 99% (21% complete (CR), 40% very good partial (VGPR), and 38% partial (PR)). The ORR post-ASCT was 78% (CR 27%, VGPR 37%, PR 14%). There was no significant difference in response between risk categories after transplant (P=0.72). At 1-year follow-up, 10 (12%) patients had relapsed and 7 (9%) patients had progression of the disease. 3 (4%) patients died of progressive MM, one of which had progressed to plasma cell leukemia. Response to treatment before and after the ASCT are summarized in Table 1.2 and Figure 1. The time to second-line treatment among patients with relapse/progression was 7 months [IQR: 3.75-10.25]. Conclusion: Here we report the demographics and outcomes of patients with MM undergoing modern modality treatments and ASCT, at our center over the last year. The median time to transplant was 6.5 months after induction therapy, and the ORR post-ASCT was 78%. No significant difference in response was observed between high and standard risk categories. No transplant-related mortality was observed as well. Figure 1 Figure 1. Disclosures Anwer: Allogene Therapeutics: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding; GlaxoSmithKline: Research Funding.

Download Full-text

Real-World Clinical Outcomes By Cytogenetic Risk Category in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽

10.1182/blood.v128.22.4784.4784 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4784-4784

Author(s):

Huamao Mark Lin ◽

Keith L Davis ◽

James A. Kaye ◽

Katarina Luptakova ◽

Lu Gao ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Research Funding ◽

Complete Response ◽

Line Treatment ◽

Second Line ◽

High Risk Patients ◽

Risk Patients ◽

Standard Risk

Abstract INTRODUCTION: Multiple Myeloma (MM) is an incurable hematologic cancer characterized by multiple recurrences. With each recurrence, patients have a lower probability of response and duration of response is shorter. Therefore, there is an unmet need to improve outcomes in relapsed/refractory multiple myeloma (RRMM). There is a shortage of data describing clinical features and outcomes in these patients in real-world practice, particularly with regard to differences in outcomes by baseline cytogenetic risk. To help address this information gap, this study analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective observational review of medical records was conducted in a cohort of 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients could be alive or deceased at the time of record abstraction. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were assessed for treatment response, overall survival (OS) and progression-free survival (PFS) from date of first relapse (study index date). All analyses were descriptive. Survival was assessed using the Kaplan-Meier (K-M) method. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. A total of 55 high-risk and 113 standard-risk patients were identified; risk category was unknown or unassessed for 32 patients. Among all patients, mean (SD) age at RRMM diagnosis was 66.3 (8.9) years and 62% of the sample was male. Lenalidomide + dexamethasone was the most common second-line systemic regimen initiated (50% of high-risk patients, 59.5% of standard-risk patients receiving second-line treatment). A total of 114 patients (57%) initiated a third-line treatment. Despite clinical response in second-line treatment occurring sooner in high-risk patients (median: 106 days) than in standard-risk patients (median: 237 days), physician-assessed overall response rate (ORR) was lower in high-risk patients (63%: 17% complete response, 46% partial response) than standard-risk patients (91%: 26% complete response, 65% partial response) across all second-line treatments combined (Table 2).. For third-line treatment, ORR was lower in high-risk patients (54%: 12% complete response, 42% partial response) than standard-risk patients (74%: 9% complete response, 65% partial response). Among patients who initiated a second-line treatment (n = 192), 47.4% were deceased at the time of data collection. From second-line initiation, K-M estimates of 1- to 5-year OS and PFS were substantially lower for high-risk patients versus standard-risk. Specifically, the proportions of patients still alive 1, 3, and 5 years after second-line treatment initiation were 73%, 51%, and 36%, respectively, for high-risk patients and 94%, 73%, and 61% for standard-risk patients. The proportions of patients without disease progression at 1, 3, and 5 years after second-line initiation were 48%, 13.5%, and 5% for high-risk patients and 82%, 42%, and 14% for standard-risk patients. CONCLUSIONS: The importance of cytogenetic risk classification as a prognostic factor in RRMM was apparent in this retrospective review, in which patients with high-risk cytogenetics had less favorable outcomes in terms of ORR, OS, and PFS than standard-risk patients. Decreased response rate and lower PFS and OS was documented among patients with high-risk cytogenetics, which is in contrast to shorter time needed to achieve best clinical response in this subgroup. Results from this real-world study provide further confirmation of the unmet medical need presented by RRMM, especially for patients with high-risk cytogenetics. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

Download Full-text

Cytogenetic Characteristics and Outcomes of Patients Receiving CTL019 CAR T Cell Therapy

Blood ◽

10.1182/blood-2019-130060 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1464-1464 ◽

Cited By ~ 2

Author(s):

Allison Barz Leahy ◽

Kaitlin J. Stanley ◽

Regina M. Myers ◽

Amanda M. DiNofia ◽

Lisa Wray ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Research Funding ◽

Risk Category ◽

Intermediate Risk ◽

Car T Cell ◽

Advisory Boards ◽

Significant Difference ◽

Car T ◽

Scientific Advisory

Background: CTL019 is a therapy derived from autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) that was approved by the FDA in August 2017 (tisagenlecleucel). Complete and durable remissions have been seen in the setting of pediatric and young adult patients with relapsed and refractory B cell acute lymphoblastic leukemia (ALL) (Maude NEJM 2018). Initial case reports suggested that there may be differential outcomes mediated by cytogenetic characteristics of the leukemia at CAR T cell infusion. Here, we report results from a single institution experience of 112 patients. Methods: Patients with relapsed/refractory ALL were identified as having received CTL019 either in the context of a clinical trial (NCT02906371) or commercial product (tisagenlecleucel) at Children's Hospital of Philadelphia from October 2016 to April 2019. Patients who received prior CAR T therapy were excluded. Demographic, cytogenetic, and outcome data were manually abstracted from the medical record or clinical trial datasets. High risk lesions were defined as MLL(KMT2A) rearrangements, Philadelphia-chromosome (Ph+), Ph-like, hypodiploidy, and TCF3/HLF fusion. Favorable cytogenetics were defined as the presence of hyperdiploidy or ETV6/RUNX1fusion and intermediate were defined as iAMP21, IKZF1deletion, or TCF3/PBX1. Patients were classified according to their highest risk cytogenetic characteristic and stratified by cytogenetic risk category present at CAR T cell infusion. Relapse-free survival (RFS) and overall survival (OS) was described for cohorts with more than 10 patients. Results: One hundred and twelve patients were included in the analysis, with a median age of 11 years (range 1-29) at infusion, of which 32% had had a previous allogeneic hematopoietic stem cell transplant (alloHSCT). Disease burden at the time of CTL019 infusion was heterogenous, with 61% having detectable disease in the bone marrow and 21% having more than 25% blasts by flow cytometry. Thirty-six patients (32%) had leukemias with high-risk genetic lesions at infusion, including 12 with MLL rearrangements and 18 with Ph+ or Ph-like lesions (Table 2). Thirty-one patients (28%) had hyperdiploidy or ETV6/RUNX1; 3 additional were in conjunction with high-risk cytogenetics (t(17;19) and 2 with Ph+), and 3 in the setting of intermediate-risk cytogenetics (iAmp21, TCF3/PBX1, IKZF1deletion). Figure 1 demonstrates RFS for those patients in remission at day 28 following infusion, stratified by cytogenetic risk category. Complete remission (CR) rate in the high-risk cytogenetics group was 94%. RFS at 12 months was 69% (0.50-0.82), 69% (0.40-0.86), and 67% (0.48-0.80) for non-informative, favorable, and high-risk cytogenetic groups, respectively. Figure 2 shows OS of patients infused with CTL019, again stratified by cytogenetic categories of interest, with a maximum follow-up time of 30 months. OS at 12 months was 84% (0.68-0.93) and 76% (0.56-0.88) for the non-informative and high-risk cytogenetic groups, respectively. There were no deaths in that time period for the favorable risk category. There was no statistically significant difference in RFS or OS for patients with high-risk cytogenetics. The intermediate-risk cytogenetics group (n<10) was excluded from these analyses. Conclusion: Durable remissions can be achieved with CTL019 across several high-risk cytogenetic subtypes of B-ALL. Stratifying outcomes by cytogenetic risk category in this unadjusted analysis does not show a statistically significant difference in either RFS nor OS. Further investigation is needed to parse out the contribution of individual cytogenetic lesions as well as the effects of other relapse and survival risk factors at play. Figure Disclosures Rheingold: Novartis: Consultancy; Pfizer: Research Funding. Callahan:Novartis: Consultancy. Hunger:Bristol Myers Squibb: Consultancy; Amgen: Consultancy, Equity Ownership; Jazz: Honoraria; Novartis: Consultancy. Grupp:Novartis: Consultancy, Research Funding; Roche: Consultancy; GSK: Consultancy; Cure Genetics: Consultancy; Humanigen: Consultancy; CBMG: Consultancy; Novartis: Research Funding; Kite: Research Funding; Servier: Research Funding; Jazz: Other: study steering committees or scientific advisory boards; Adaptimmune: Other: study steering committees or scientific advisory boards. Maude:Kite: Consultancy; Novartis: Consultancy.

Download Full-text

MyPRSR Molecular Subtypes of Multiple Myeloma Represent All High-Risk FISH Translocations Included in the mSMART 2.0 and R-ISS Guidelines

Blood ◽

10.1182/blood.v128.22.3264.3264 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3264-3264 ◽

Cited By ~ 1

Author(s):

Ryan K Van Laar ◽

Ivan Borrelo ◽

David Jabalayan ◽

Ruben Niesvizky ◽

Aga Zielinski ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

High Risk ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Research Funding ◽

Plasma Cells ◽

Molecular Subtypes ◽

Risk Status ◽

Significant Difference

Abstract Background: There is a global consensus that multiple myeloma patients with high-risk disease require additional monitoring and therapy compared to low/standard risk patients in order to maximize their chances of survival. Current diagnostic guidelines recommend FISH-based assessment of chromosomal aberrations to determine risk status (i.e. t(14;20), t(14;16), t(4;14) and/or Del17p), however, studies show FISH for MM may have a 20-30% QNS rate and is up to 15% discordant between laboratories, even when starting from isolated plasma cells. In this study we demonstrate that MyPRS gene expression profiling reproduces the key high risk translocations for MM risk stratification, in addition to having other significant advantages. Methods: Reproducibility studies show that MyPRS results are less than 1% discordant starting from isolated plasma cells and return successful results in up to 95% of cases. 270 MM patients from Johns Hopkins University (MD) and Weill Cornell Medicine (NY) had both FISH and MyPRS gene expression profiling performed between 2012 and 2016 using standard and previously published methodology, respectively. Results: Retrospective review of the matched FISH and MyPRS results showed: 25/28 (89%) patients wish FISH-identified t(4;14) were classified as MMSET (MS) subtype. 10/10 (100%) patients with t(14;16) or t(14;20) were classified as MAF-like (MF) subtype 62/67 (93%) patients with t(11;14) were assigned to the Cyclin D (1 or 2) subtype. Patients with FISH hyperdiploidy status were classified as the Hyperdiploid (HY) subtype or had multiple gains detected by the separate MyPRS Virtual Karyotype (VK) algorithm, included in MyPRS. TP53del was seen in patients with multiple molecular subtypes, predominantly Proliferation (PR) and MMSET (MS). Assessment of TP53 function by gene expression is a more clinically relevant prognostic marker than TP53del, as dysregulation of the tumor suppressor is affected by mutations as well as deletions. Analysis of the TP53 expression in the 39 patients with delTP53 showed a statistically significant difference, compared to patients without this deletion (P<0.0001). Conclusion: Gene expression profiling is a superior and more reliable method for determining an individual patients' prognostic risk status. The molecular subtypes of MM, as reported by Signal Genetics MyPRS assay, are driven by large-scale changes in gene expression caused by or closely associated with chromosomal changes, including translocations. Physicians who are managing myeloma patients and wishing to base their assessment of risk on R-ISS or mSMART Guidelines may obtain the required data points from either FISH or MyPRS, with the latter offering lower QNS rates, higher reproducibility, assessment of a larger number of cells and a substantially lower price point ($5,480 vs. $1,912; 2016 CMS data). A larger cohort study is now underway to further validate these observations. Figure GEP-based TP53 expression in patients with and without Del17p. P<0.0001 Figure. GEP-based TP53 expression in patients with and without Del17p. P<0.0001 Disclosures Van Laar: Signal Genetics, Inc.: Employment. Borrelo:Sidney Kimmel Cancer Institute: Employment. Jabalayan:Weill Cornell Medical Center: Employment. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding, Speakers Bureau. Zielinski:Signal Genetics, Inc.: Employment. Leigh:Signal Genetics, Inc.: Employment. Brown:Signal Genetics, Inc.: Employment. Bender:Signal Genetics, Inc.: Employment.

Download Full-text

Risk of Progression and Survival in Newly Diagnosed Multiple Myeloma Patients Non-Responsive to Bortezomib-Based Induction Therapy: an Observational Multicenter International Study

Blood ◽

10.1182/blood.v124.21.3488.3488 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3488-3488

Author(s):

Yael C Cohen ◽

Erel Joffe ◽

Noam Benyamini ◽

Meletios A. Dimopoulos ◽

Svetlana Trestman ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Disease Progression ◽

Line Treatment ◽

Second Line ◽

Newly Diagnosed ◽

Inclusion Criteria ◽

First Line ◽

Line Therapy ◽

Induction Regimen

Abstract INTRODUCTION Botezomib-based induction is widely used and highly effective for the treatment of patients with newly diagnosed multiple myeloma (NDMM), with an overall response rate (ORR) of 75-80%. However, the outcomes of patients who fail to respond to this treatment remain unclear. The goal of this study was to investigate the outcome of patients with NDMM who failed to respond to bortezomib-based induction as compared to induction-responsive patients. METHODS We reviewed consecutive patients with NDMM between 1-JAN-2007 and 31-JAN-2014 in three participating centers in Greece and Israel. Inclusion criteria were measurable disease and an induction regimen containing bortezomib in combination with alkylators and/or corticosteroids. Patients who failed to achieve at least partial response in accordance with IMWG criteria after 4 cycles of therapy were classified as non-responsive and their baseline characteristics, next treatment, overall survival and progression following second-line treatment (2ndPFS) were assessed and compared to responsive patients. 2ndPFS was defined as the time from 2nd line treatment to disease progression, death or censoring. In the non-responsive group we limited this analysis to patients advancing to 2nd line within six months of initiation of induction. RESULTS Two hundred and ninety five patients met inclusion criteria and 74 (25%) were non-responsive to bortezomib-containing induction. Non-responsive patients were older, more anemic and had more often ISS-3, del17p and ECOG performance status 2-4 (table 1). Notably, these patients received less often a bi-weekly bortezomib schedule, a triple-drug regimen and high dose melphalan treatment at first line. Of the non-responsive patients 57% (n=42) received salvage treatment immediately following induction non-response, with an ORR of 59% (25/42); 12/31(39%) of those treated with salvage 2nd line and 13/15(87%) of those who underwent HDM at first line, responded. Failure to respond to bortezomib induction was associated with increased mortality (HR 5.06, 95% CI 2.80 – 9.16) (Fig. a), which remained significant in multivariate analysis. One- and 3-years OS in responsive vs. non-responsive patients were 97% vs 76% and 88% vs 53%, respectively (p<0.0001). 2ndPFS in patients who received salvage second line therapy immediately following induction failure was similar to that measured in bortezomib-responsive patients receiving 2nd-line therapy for disease progression, approaching 14 months. However, survival from time of salvage 2nd-line treatment was significantly lower among patients non-responsive to bortezomib-based induction compared to that measured in responsive patients (25 months vs. not reached, respectively, p=0.024; Fig. b). CONCLUSIONS Failure to respond to a bortezomib-based induction was found to be an independent risk factor for mortality. Despite the non-inferior 2ndPFS reported in these patients as compared with their bortezomib-responsive counterparts, survival remained significantly inferior. Possibly this difference is because non-responsive patients are less likely to respond to further proteasome inhibitor therapy at following relapses. Randomized controlled trials are needed to test whether intensification of induction and/or of further treatment may improve the poor prognosis of patients who fail to respond to bortezomib-based induction. Table 1: All patients n = 295 Induction non-responsive n = 74 Induction - responsive n =221 P value Demographic Median Age (yrs) 62.0 66.8 61.0 0.004 Gender Male Female 148 (50%) 147 (50%) 42 (55%) 33 (45%) 107 (48%) 114 (52%) 0.347 Patient / Disease ECOG 0-1 2-4 182 (63%) 107 (37%) 33 (45%) 40 (55%) 149 (69%) 67 (31%) <0.0001 ISS I II III 74 (28%) 95 (36%) 95 (36%) 9 (14%) 20 (33%) 33 (53%) 65 (32%) 75 (37%) 62 (31%) 0.002 High risk Cytogenietics Del17p High risk (%) Elevated LDH (%) Extramedullary disease (%) Hb≤ 10 gr% Creatinine > 2mg% 23 (14%) 69 (34%) 66 (27%) 23 (9.5%) 114 (43%) 64 (23%) 10 (26%) 13 (28%) 21 (36%) 5 (8.1%) 35 (54%) 20 (30%) 13 (10%) 56 (36%) 45 (24%) 18 (9.7%) 79 (39) 44 (21%) 0.031 0.297 0.091 0.805 0.044 0.094 Therapy Induction regimen VCD Vd VMP PAD 204 (69%) 49 (17%) 11 (4%) 19 (6%) 52 (57%) 18 (24%) 3 (4%) 4 (5%) 162 (73%) 31 (14%) 8 (4%) 15 (7%) 0.007 Any triplet 243 (82%) 55 (74%) 188 (85%) 0.051 Bortezomib schedule Bi-weekly Weekly 239 (81%) 56 (19%) 52 (70%) 22 (30%) 187 (85%) 34 (15%) 0.010 HDM at first line 143 (48%) 15 (20%) 128 (58%) <0.0001 Figure 1 Figure 1. Disclosures Dimopoulos: Celgene: Consultancy, Honoraria.

Download Full-text

Phase 2 Study of Carfilzomib, Thalidomide, and Low-Dose Dexamethasone As Induction/Consolidation in Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma, the Carthadex Trial

Blood ◽

10.1182/blood.v128.22.1141.1141 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1141-1141 ◽

Cited By ~ 6

Author(s):

Ruth Wester ◽

Bronno van der Holt ◽

Emelie Asselbergs ◽

Mark van Duin ◽

Sonja Zweegman ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Induction Therapy ◽

Research Funding ◽

Fixed Dose ◽

Phase 2 ◽

Newly Diagnosed ◽

Significant Difference ◽

Standard Risk

Abstract Introduction A phase 2 dose escalation trial of Carfilzomib in combination with Thalidomide and Dexamethasone (KTd) for induction and consolidation in newly diagnosed, transplant-eligible patients with multiple myeloma (MM). We report the results of 4 dose levels. Methods In this multicenter, open-label, phase 2 trial, transplant-eligible patients aged between 18 and 65 years with previously untreated symptomatic MM were included. Patients were treated with 4 cycles of escalating dose of Carfilzomib + fixed-dose thalidomide and dexamethasone (KTd) for induction therapy. The dose of Carfilzomib was 20 mg/m2 i.v. on days 1, 2 followed by 27 mg/m2 on days 8, 9, 15, 16 of cycle 1 and on days 1, 2, 8, 9, 15 and 16 of cycles 2 to 4. Thalidomide dose was 200 mg orally on days 1 through 28 and Dexamethasone 40 mg orally on days 1, 8, 15 and 22. Carfilzomib was escalated to 20/36 mg/m2 in cohort 2, to 20/45 mg/m2 in cohort 3 and to 20/56 mg/m2 in cohort 4. Induction was followed by stem cell harvest after Cyclophosphamide priming (2 to 4 mg/m2) and G-CSF. Hereafter patients received high-dose Melphalan (HDM, 200mg/m2) and autologous stem cell transplantation followed by consolidation treatment with 4 cycles of KTd in the same schedule except a lower dose of Thalidomide (50mg). The primary endpoint was response after induction therapy and overall, specifically complete response (CR) and very good partial response (VGPR). Secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). Results All 111 patients with a median follow-up of 55, 42, 35 and 28 months, in cohorts 1 to 4, respectively were included in the analysis. Median age was 58 years. ISS stages I/II/III were 41%/34%/23%, respectively, R-ISS stages I/II/III/unknown were 23%/59%/9%/9%, respectively. Of 111 patients, 9 patients stopped treatment during/after induction, 8 patients after cyclophosphamide priming or HDM and 9 patients during consolidation because of toxicity (n=9), non-eligibility for further treatment (n=6), progression (n=5), refusal (n=2) or other reasons (n=4). Overall response rate for all cohorts was 95%. Response after induction was CR/sCR in 18% of patients, ≥ VGPR in 66% of patients, ≥ PR in 94% of patients. After HDM the CR/sCR rate increased to 31% and after consolidation to 64%. Responses between cohorts were in general comparable. See Table 1. Response based on risk status by ISS/FISH in either cohort and accumulated did not show a difference in CR/sCR rate after consolidation between standard-risk (67%) and high risk defined as t(4;14) and/or del17p and/or add1q and/or ISS3 (60%). OS at 30 months was comparable between standard risk and high risk, 91% versus 90%. PFS at 30 months for standard risk and high risk was 79% and 62%, logrank p=0.02 (HR=2.3, 95% CI=1.1-4.5). PFS at 30 months per cohort was 70% (95% CI, 55% to 81%), 70% (95% CI, 45% to 85%), 80% (95% CI, 56% to 92%) and 62% (95% CI, 32% to 82%) in cohorts 1,2, 3 and 4, respectively, and 71% (95% CI, 61% to 79%) in all patients. OS at 30 months per cohort was 90% (95% CI, 77% to 96%), 90% (95% CI, 66% to 97%), 95% (95% CI, 71% to 99%) and 88% (95% CI, 58% to 97%) respectively, and 91% (95% CI, 83% to 95%) in all patients. Gene expression profiling using the Affymetrix U133 Plus 2.0 GeneChips was performed on purified tumor cells for 49 patients. Using the prognostic classifier EMC92 a high-risk group of patients (16%) was identified versus standard risk (in terms of OS: logrank p=0.06 (HR=3.7, 95% CI=0.8-16.8), and in terms of PFS: logrank p=0.14 (HR=2.1, 95% CI=0.8-6.0)). Safety analysis for all 111 patients showed non-hematological grade 3 and 4 toxicity, mainly respiratory disorders (in 15%), GI disorders (13%) and skin lesions (10%). Toxicity between cohorts did not show a significant difference. Cardiac adverse events were limited and included heart failure (n=2 at 27 mg/m2), hypertension (n=2) and chest pain (n=1 at 45mg/m2). Conclusion Carfilzomib, thalidomide, dexamethasone (KTd) is an effective regimen, with increasing CR percentages following KTd consolidation. With escalated doses of Carfilzomib responses and toxicity were comparable to standard dose of 27 mg/m2. Disclosures Zweegman: Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Kersten:Celgene: Research Funding; Amgen: Honoraria. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Lokhorst:Genmab: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Broijl:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Sonneveld:Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

Download Full-text

Improved Survival of Patients with Myelofibrosis in the Last Decade

Blood ◽

10.1182/blood-2020-142578 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 50-51

Author(s):

Lucia Masarova ◽

Prithviraj Bose ◽

Naveen Pemmaraju ◽

Lingsha Zhou ◽

Sherry A. Pierce ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Research Funding ◽

Myeloproliferative Neoplasm ◽

Categorical Variables ◽

Rank Test ◽

Fisher Exact Test ◽

Grant Support ◽

Before And After

Introduction: The myeloproliferative neoplasm myelofibrosis (MF) is associated with reduced overall survival (OS) compared to the general population. In 2011, the JAK1/2 inhibitor ruxolitinib, was approved in the USA for the treatment of intermediate and high-risk MF. Long-term follow-up of patients in pivotal phase 3 studies showed survival benefit of ruxolitinib therapy. Objective: We sought to evaluate the outcome of patients with MF diagnosed before and after the year of 2010 to assess whether OS changed in the past decade in the era of ruxolitinib. Methods: We retrospectively reviewed the charts of 1346 patients with MF who presented to our institution in the last 25 years and compared clinical parameters and outcomes between those presented before and after the year of 2010 (before / after y. 2010). Newly diagnosed MF patients and patients within 12 months from diagnosis who were previously only treated with supportive therapy (danazol, growth-factors, steroids) were included. Cytogenetics (≥10 metaphases) was classified according to Gangat, JCO, 2011. Molecular analysis (≥ 28 genes) was performed only after y. 2010 by using next generation sequencing platform. Fisher exact test and χ2 were used for analysis of categorical variables. Overall survival (OS) was estimated using the Kaplan-Meier method and comparison was done by the log-rank test. Results: Among the 1346 patients, 806 (60%) patients were seen after y. 2010. Median age of all patients was 65 years (range, 20-94), 62% were males. Patient characteristics with comparison between groups are shown in Table 1. Patients after y. 2010 were older, with lower WBC and lower lactate dehydrogenase, but had more symptoms. The distribution of IPSS scores between groups were comparable at around 10% for low, 36% for intermediate-1, 20-25% for intermediate-2 and ~30% for high risk. Eighty-five and 80% of patients before and after y. 2010, respectively, received therapy for MF at our institution. Overall, 78 patients (37 after y. 2010) underwent stem cell transplantation. Among treated patients at our institution, 25% (n 117) and 37% (n 241) before and after y. 2010 received ruxolitinib during their follow-up. Ruxolitinib therapy was initiated with a median time of 2 months (range, 0.2-156) from presentation to our institution, longer in those before y. 2010 (11 vs 1 months in patients after y. 2010, respectively, p = 0.001) After a median follow-up of 30.4 months (range, 0.9-266); 659 (49%) of patients died. More deaths were noticed in those before y. 2010 (74% vs 32 %, respectively, p < 0.001); but these patients had also longer follow-up (37.5 months vs 25 months, p < 0.001). Eighty-five patients (10%) developed acute leukemia: 2 cases per 100 person-years per observation for both groups. Patients after y. 2010 had superior OS to those before y. 2010 with HR 0.7 (95% CI: 0.59-0.82), p < 0.001, Figure 1. Superior OS was observed in all patients after y. 2010 (vs before y. 2010) when stratified by IPSS score (higher equals for combination of int -2 and high, Figure 2), or age (cutoff of 65 years, Figure 3). Patients exposed to ruxolitinib had superior OS regardless of being diagnosed before or after y. 2010, with respective medians of 98 (95% CI: 78-118) and 91 (95% CI: 73-109) months (details to be presented at the conference). Conclusion: Our results demonstrate that survival of patients with MF has improved in the last decade. Survival has improved in younger and older patients as well as in those with more advanced disease (per IPSS risks). Many factors may have contributed to the observed improvement in outcome of MF patients, including new therapies, e.g. ruxolitinib, as well as improved supportive management and disease awareness. Disclosures Bose: Blueprint Medicines Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; NS Pharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Honoraria, Research Funding; Promedior, Inc.: Research Funding. Pemmaraju:Daiichi Sankyo: Research Funding; DAVA Oncology: Honoraria; Blueprint Medicines: Honoraria; Roche Diagnostics: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Honoraria; Incyte Corporation: Honoraria; MustangBio: Honoraria; Plexxikon: Research Funding; Samus Therapeutics: Research Funding; SagerStrong Foundation: Other: Grant Support; Novartis: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; LFB Biotechnologies: Honoraria; Stemline Therapeutics: Honoraria, Research Funding; Cellectis: Research Funding. Kantarjian:Novartis: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; Astex: Research Funding; Takeda: Honoraria; Agios: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding. Verstovsek:CTI Biopharma Corp: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; ItalPharma: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; AstraZeneca: Research Funding.

Download Full-text

Treatment of Relapsed and Refractory Multiple Myeloma with Fully Oral Triplet IRD (ixazomib, lenalidomide and dexamethasone) Is Safe and with Significant Therapeutic Outcomes

Blood ◽

10.1182/blood-2018-99-112046 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1959-1959 ◽

Cited By ~ 2

Author(s):

Jiri Minarik ◽

Petra Krhovska ◽

Tomas Jelinek ◽

Alexandra Jungova ◽

Martin Mistrik ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Board Of Directors ◽

Research Funding ◽

Statistical Significance ◽

Categorical Variables ◽

Cell Transplant ◽

Advisory Committees ◽

Extramedullary Plasmocytoma

Abstract Aims: Treatment of multiple myeloma (MM) in relapsed and refractory setting (RRMM) has been a challenge. The best outcomes have been observed in triplet combination of novel drugs. However, most combinations require weekly parenteral administration thus degrading patients´adherence to therapy, especially when treatment is scheduled "until progression". The introduction of fully oral triplet combination ixazomib, lenalidomide and dexamethasone (IRD) showed an outstanding efficacy in the Tourmaline-MM1 trial. Our aim is to determine the efficacy and safety of IRD regimen outside clinical trials. Patients and methods: A cohort of 127 RRMM patients from the Czech and Slovak Republic were treated with IRD regimen within a Named Patient Program between 2016 and 2018. The M/F ratio was 1.2:1 with median age 66 years (41-84). The representation of M-protein and light chain types as well as ISS stage was standard. The data for cytogenetics were recorded only at the time of diagnosis in 71% of patients with 15 patients having high-risk features - t(4;14), t(14;16) and del17, and 41 patients having standard risk features. In 34 patients we were not able to determine the risk status as at least one abnormality was missing and none was positive. The presence of extramedullary plasmocytoma was recorded in 15% of patients. Most patients received IRD for their 1st relapse (58.5%), followed by 2nd (23.7%) and 3rd relapse (7.6%) with significant portion of patients being treated in ≥4th relapse (10.1%). The pretreatment with individual drugs was as follows: bortezomib (BTZ) 94.5%, thalidomide (THAL) 40.9%, lenalidomide (LEN) 18.9% and carfilzomib 5.5%. 62.2% of patients underwent previous autologous stem cell transplant. Altogether 25.2% of patients were refractory to at least 1 drug with 18.9% being BTZ refractory and 7.9% LEN refractory. Data were analyzed from the Czech Registry of Monoclonal Gammopathies. Data were described by absolute and relative frequencies of categorical variables and mean (standard deviation), median (minimum-maximum) of quantitative variables. Survival measures were plotted using Kaplan-Meier methodology at 95% confidence interval, log-rank test was used to estimate the statistical significance at P<0.05. Results: The overall response rate to IRD regimen (≥ partial response, PR) was 67.1% with clinical benefit rate (≥ minimal response, MR) of 77.2%. The rate of individual responses was as follows: complete response (CR) in 11.4%, very good partial response (VGPR) in 16.5%, PR in 39.2%, MR in 10.1%, stable disease (SD) in 13.9% and progressive disease (PG) in 8.9%. The median overall survival was not reached after median follow up of 9.4 months. Median progression free survival (PFS) was 23.1 months. PFS was significantly decreasing with number of previous lines (not reached after 1 previous lines, 23.1 after 2 lines, 8.7 after 3 lines and 4.6 after ≥4 lines, p = 0,006). As expected, the best PFS increased with deeper therapeutic response (SD+PD = 4.1 months, MR = 9.0 months, PR = 15.1 months, VGPR = 13.2 months, and CR = median PFS not reached). There were limited information regarding the high risk features. Still, we confirmed adverse impact of the presence of extramedullary disease (PFS 5.5 vs 23.1 months, p = 0.001). Similarly, patients did worse when being pretreated by both proteasome inibitor and an IMiD versus solely proteasome inhibitor (PFS 10.0 vs 23.1 months, p = 0.001). The outcomes of high-risk cytogenetics were beyond statistical significance. Most toxicities were grade ≤2. Only hematological toxicity and infection reached grade 3 or higher, as follows: neutropenia in 35.1%, thrombocytopenia in 22.8%, anemia in 12.3% and infection in 19.3%. Conclusions: IRD regimen is very effective in RRMM. We confirmed its efficacy even in highly pretreated population (≥4 prior regimens) and in patients refractory to BTZ or LEN, which were exclusion criteria for the Tourmaline trial. The fully oral combination is well tolerated, with manageable side effects and easy management of dose modifications. Unlike the original trial our data show better results in patients with less pretreatment. The presence of extramedullary plasmocytoma deteriorates the prognosis of patients on IRD regimen. We thank to Takeda for enabling the Named Patient Program. With support of AZV 17-29343A, MH CZ - DRO (FNOl, 00098892) Disclosures Maisnar: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Hajek:Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Research Funding.

Download Full-text

Real-World Treatment Patterns and Health Care Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽

10.1182/blood.v128.22.5945.5945 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5945-5945 ◽

Cited By ~ 1

Author(s):

Huamao Mark Lin ◽

Keith L Davis ◽

James A. Kaye ◽

Katarina Luptakova ◽

Lu Gao ◽

...

Keyword(s):

High Risk ◽

Disease Progression ◽

Research Funding ◽

Line Treatment ◽

Second Line ◽

Risk Patients ◽

First Relapse ◽

Third Line ◽

Standard Risk ◽

Third Line Treatment

Abstract INTRODUCTION: Despite the introduction of numerous novel agents and treatment strategies leading to improved response rates and overall survival, virtually all patients with multiple myeloma (MM) eventually relapse. While relapsed and/or refractory multiple myeloma (RRMM) remains an area of unmet need, little data have been generated describing typical treatment patterns and resource utilization in these patients. To help address this information gap, we analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective medical record review was conducted in 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable or unassessed; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were retrospectively assessed on second- and third-line treatment regimens received, treatment duration and reasons for discontinuation, and subsequent health care utilization from date of first relapse (study index date). All analyses were descriptive. RESULTS: Demographic and clinical characteristics are presented in Table 1. Altogether 55 high-risk and 113 standard-risk patients were selected; risk category was unknown for 32 patients. Among the 200 patients studied, 192 (96%) received ≥1 additional line of systemic chemotherapy after first relapse; 114 patients (57%) received ≥2 additional lines of systemic therapy (i.e., at least second- and third-line therapy). The most common second-line regimen was lenalidomide + dexamethasone (54%), followed by bortezomib + dexamethasone with or without a third agent (23%). Median duration of second-line treatment was 9 cycles over 9.4 months. Most patients (92%) discontinued second-line treatment, most commonly due to disease progression (37%), to reaching complete clinical response with no additional benefit expected (33%), to lack/loss of response (13%), or to toxicities/adverse events (8%). Among the 114 patients receiving a third-line treatment, regimens were more varied; bortezomib + dexamethasone with or without other third agents was the most common third-line regimen (27%). Median third-line duration (across all regimens) was 6 cycles over 5.9 months. The leading reason for third-line treatment discontinuation was disease progression (42%), followed by attainment of complete response with no addition benefit expected (21%). During the follow-up period from RRMM diagnosis until death or last medical record, 35% of patients had ≥1 hospitalization, with high-risk patients having a higher hospitalization incidence than standard-risk patients (34 vs. 15 admissions per 100 person-years; p<0.05); a similar disparity was observed for emergency department utilization (25 vs. 15 visits per 100 person-years; p<0.05). Leading clinical burdens included bone pain (58%), fatigue/weakness (75%), impairment of daily activities (59%), anemia (55%), thrombocytopenia (44%), and neutropenia (40%). CONCLUSIONS: Lenalidomide + dexamethasone was the most commonly observed second-line regimen in this medical record review. Second-line treatment duration was generally less than a year, which indicates an unmet need in these patients, particularly in light of the primary reasons cited for unplanned discontinuation (disease progression, loss of response, no perceived additional benefit, and toxicities). Hospitalizations and emergency department visits were common among these patients after first relapse, indicating a potentially high cost burden of disease, particularly for patients with high-risk cytogenetic abnormalities in whom health care utilization was generally higher than for patients with standard-risk disease. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

Download Full-text

Impact of Corticosteroids on Efficacy of BCMA Targeted CAR-T Therapy in Multiple Myeloma

Blood ◽

10.1182/blood-2021-146678 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1759-1759

Author(s):

Eva Duvalyan ◽

Mimi Lo ◽

Thomas Martin ◽

Jeffrey L. Wolf ◽

Alfred Chung ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

Research Funding ◽

Disease Burden ◽

Cell Activity ◽

Categorical Variables ◽

Steroid Use ◽

Steroid Dose ◽

Significant Difference ◽

Car T

Abstract Background: B-cell maturation antigen (BCMA) directed chimeric antigen receptor T-cell therapy (CAR-T) has shown unprecedented efficacy in multiple myeloma (MM). CAR-T toxicities in the acute period, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and macrophage activation syndrome (MAS) are managed by tocilizumab, steroids, and/or anakinra. However, since steroids have been shown to inhibit T cell activity (Ashwell et al. 2000), their use to mitigate these toxicities may have deleterious effects on CAR-T efficacy. Previous studies which examined steroid effects on CAR-T therapy in other hematologic malignancies have shown mixed results (Liu et al. 2020, Strati et al. 2021, Topp et al. 2019). We performed a single-center retrospective analysis of steroid use in MM patients (pts) during BCMA CAR-T hospitalization. Methods: All patients treated at UCSF with a BCMA CAR-T for MM from 11/1/2017-3/31/2021 were analyzed for steroid use during CAR-T hospitalization and treatment outcomes. Per institutional policy, all CAR-T pts were hospitalized for at least 14 days post-CAR-T infusion. Baseline pt characteristics, steroid usage, CAR-T toxicities and its treatment were collected. Overall response rate (ORR) was determined according to International Myeloma Working Group criteria. Overall survival (OS), progression-free survival (PFS) and time-to-next treatment (TTNT) were summarized using Kaplan-Meier methods and compared using log-rank tests. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical variables, respectively. Results: Of the 62 CAR-T pts, 24 (38.7%) received steroids during CAR-T hospitalization. Fifteen (62.5%), 5 (20.8%), 1 (4.2%) and 3 (12.5%) pts were given steroids respectively for CRS only, CRS and ICANS, CRS and MAS, or ICANS only. CAR-T toxicities included: 52 pt with CRS (27 gr 1, 25 gr 2); 8 pt with ICANS (3 gr 1, 3 gr 2, 2 gr 3) and 9 pt with MAS (3 gr 1, 2 gr 2, 3 gr 3, 1 gr 4). All pts received only dexamethasone (dex) except for 1 for whom solumedrol was converted into dex equivalent units. Median time to steroid initiation after CAR-T infusion was 2 days (0-10), median total days on steroids was 4 (1-10), and median cumulative steroid dose was 60mg (10-498). Overall, the results showed no significant difference in ORR (95.8% v 84.2, p=0.2), PFS (13.1 v 13.2 mo, p=0.9) (Fig. 1A), OS (not reached (NR) v 26.4 mo, p=0.5) (Fig. 1B) or TTNT (10.5 v 7.0, p=0.3) when pts received steroids compared to no steroids. There were also no significant differences in ORR, PFS, OS, or TTNT based on cumulative dose of steroid received. Pts given 0 v ≤ 60 v > 60mg cumulative steroid dose had ORR of 84.2%, 100%, 90.9% (p=0.4) and median PFS of 13.2, 15.7 and 13 mo (p=0.5) (Fig. 1C), respectively. Similarly, median OS (Fig. 1D) and TTNT was 26.3 mo, NR, NR (p=0.6) and 22.8, 17.5, 15.1 mo (p=0.6) for the three groups, respectively. Pts who received steroids for 0 vs 1-5 vs ≥5 days had ORR of 84.2%, 100% and 85.7% (p=0.2). There was no statistically significant difference in median PFS (13.2, 21.4, and 10.6 mo (p=0.05)) (Fig. 1E) or median OS (26.4, NR, and 24.8 mo (p = 0.2)) (Fig. 1F). Median TTNT was statistically significant at 22.8, 24.6, and 12.5 mo (p = 0.04). Median length of hospitalization was 14 days for both steroid-treated and non-steroid treated pts. Median disease burden (as measured by pre-CAR-T serum free light chains (SFLC)) also did not differ based on steroid treatment (195.9 mg/L vs 207.5 mg/L, p=0.9). Median follow-up time for the whole cohort was 19.0 mo (range 1.2-42.9). Forty-three (69%) pts died and 36 (58%) pts progressed through CAR-T. Lastly rates and timing of CRS, ICANS, and MAS, as well as tocilizumab and anakinra doses, initiation dates, and duration were not significantly associated with worsened ORR, PFS or OS. Pts with a high (>207.5 mg/L) pre-CAR-T SFLC were associated with a shortened PFS (10.6 v 35 mo, p=0.002) (Fig. 2A), OS (24.2 mo v NR, p=0.07) (Fig. 2B) and TTNT (11.9 v 41.4 mo, p=0.002) compared to those with low disease burden (≤207.5 mg/L). Conclusions: In conclusion, our retrospective study showed that steroid use in general is not significantly associated with worsened ORR, PFS, OS, and TTNT in pts receiving BCMA targeted CAR-T for MM. There may be an impact on PFS and TTNT when the total time on steroids is ≥ 5 days. Future larger studies are needed to examine the effect of steroid exposure and duration on BCMA CAR-T efficacy. Figure 1 Figure 1. Disclosures Lo: Oncopeptides: Consultancy; EUSA Pharma: Consultancy. Martin: GlaxoSmithKline: Consultancy; Amgen: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Sanofi: Research Funding. Wolf: Adaptive Biotechnologies: Consultancy; Teneobio: Consultancy; Sanofi: Consultancy; Amgen: Consultancy. Chung: Caelum: Research Funding. Shah: Nektar: Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding; Kite: Consultancy; Sanofi: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Karyopharm: Consultancy; Precision Biosciences: Research Funding; Indapta Therapeutics: Consultancy; GSK: Consultancy; CSL Behring: Consultancy; CareDx: Consultancy; BMS/Celgene: Research Funding; Bluebird Bio: Research Funding; Amgen: Consultancy; Teneobio: Research Funding. Wong: Amgen: Consultancy; Genentech: Research Funding; Fortis: Research Funding; Janssen: Research Funding; GloxoSmithKlein: Research Funding; Dren Biosciences: Consultancy; Caelum: Research Funding; BMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Outcomes and Clinical Features of Patients with 1q+ Multiple Myeloma Treated with Lenalidomide, Bortezomib, and Dexamethasone

Blood ◽

10.1182/blood-2018-99-112216 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3241-3241 ◽

Cited By ~ 1

Author(s):

Timothy M. Schmidt ◽

Nisha Joseph ◽

Levani Odikadze ◽

Leonard Heffner ◽

Craig C Hofmeister ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Board Of Directors ◽

Induction Therapy ◽

Research Funding ◽

Large Population ◽

Chromosome 1 ◽

Advisory Committees ◽

Significant Difference

Abstract Introduction: Recurrent cytogenetic abnormalities have been well described in multiple myeloma and have important roles in the development and progression of myeloma, as well as prognostic implications for patient survival. Amplification of chromosome 1 (+1q) has been associated with inferior outcomes including survival. However, it is unclear whether this association is due to a primary effect of +1q on myeloma biology or secondary to its association with genomic instability and more advanced disease. Furthermore, the prognostic implication of +1q has yet to be determined in the setting of novel treatment regimens including triplet induction regimens incorporating an immunomodulatory agent and proteasome inhibitor backbone, with consideration of risk-adapted maintenance therapy. This study investigated the clinical characteristics and outcomes of a large population of multiple myeloma patients with +1q who were treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy. Methods: We collected data for 1000 patients with newly diagnosed multiple myeloma who received RVD induction and were seen at Emory University/Winship Cancer Institute between July 1, 2005 and August 31, 2016. Baseline characteristics were determined, including age, sex, race, laboratory values at diagnosis (hemoglobin, creatinine, calcium, albumin, lactate dehydrogenase, beta-2-microglobulin, isotype, paraprotein, and serum free light chains) and molecular cytogenetics by fluorescent in-situ hybridization (FISH) for +1q, t(11;14), t(4;14), t(14;16), del(17p), del(13q), and hyperdiploidy. Patients were also categorized by their ISS stage, high-risk cytogenetics (defined as t(4;14), t(14;16), or del(17p)), and whether they were treated with autologous stem cell transplantation (ASCT). The primary outcomes were response to RVD induction by IMWG criteria (complete response (CR), very good partial response (VGPR), and partial response (PR)), progression free survival (PFS), and overall survival (OS) of patients with +1q compared to patients without +1q. Hazard ratios and p-values for PFS and OS were calculated using multivariate analysis accounting for presence of ISS stage 3 disease, t(4;14), t(14;16), and del(17p). Results: Of 1000 total myeloma patients treated with RVD induction, 146 (14.6%) were noted to have +1q by FISH. Patients with +1q, compared to those without +1q, were more likely to be Caucasian (75.2% vs 60.1%, p=0.001) , have IgA isotype (29.8% vs 18.6%, p=0.049) , present with calcium > 10.5 (22.8% vs 14.3%, p=0.026) , and have concurrent high-risk abnormalities by FISH (59.6% vs 21.7%, p<0.001) . There was no significant difference in response to RVD induction, with responses of ≥CR/≥ VGPR /≥PR of 42.2%/67.2%/99.3% for patients with +1q compared with 36.1%/68.8%/97.8% for patients without +1q (p=0.693) . Median PFS was significantly shorter for patients with +1q compared with those without +1q (41.8 months vs 86.0 months , respectively, HR 2.39, p<0.001 ). OS of patients with +1q was significantly worse than patients without +1q (median not reached, HR 2.316, p=0.001 ). Conclusion: In this retrospective, single-center analysis of multiple myeloma patients treated with RVD induction, patients with 1q amplification had similar responses to induction therapy, but significantly inferior PFS and OS compared to patients without +1q. Further investigation is required to determine if the timing of 1q gain, copy number of chromosome amplification, and/or association with other high-risk cytogenetics are important contributing factors to the prognosis of patients with +1q. Disclosures Heffner: ADC Therapeutics: Research Funding; Kite Pharma: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding. Hofmeister:Bristol-Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Boise:AstraZeneca: Honoraria; Abbvie: Consultancy. Lonial:Amgen: Research Funding. Nooka:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kaufman:Karyopharm: Other: data monitoring committee; Janssen: Consultancy; Abbvie: Consultancy; Roche: Consultancy; BMS: Consultancy.

Download Full-text