Outcomes of patients with t(11;14) multiple myeloma: An International Myeloma Working Group (IMWG) multicenter study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8015-8015 ◽  
Author(s):  
Brian G. Durie ◽  
Hartmut Goldschmidt ◽  
Maria-Victoria Mateos ◽  
Veronica Gonzalez ◽  
Juan Du ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multicenter Study ◽  
Response Duration ◽  
Initial Therapy ◽  
Survival Outcomes ◽  
Cell Transplant ◽  
Entire Cohort ◽  
Drug Classes ◽  
Line Of Therapy

8015 Background: Multiple myeloma (MM) is a heterogeneous disease with varying survival outcomes depending on the presence of certain genetic abnormalities. Common abnormalities include trisomies, translocations involving chromosome 14, and amplifications or deletions of chromosomes 1, 13, and 17. t(11;14), occurring in approx. 15% of patients (pts) with MM, is considered a standard risk abnormality, but recent data suggest that the prognosis may be inferior to what had been expected. This is of particular relevance as new therapeutic options such as the BCL-2 inhibitor venetoclax has been shown to be effective in t(11;14) pts. Methods: This was a multicenter study designed and conducted by the IMWG, to identify the outcomes of pts with t(11;14) using a retrospective cohort of pts. Pts with MM diagnosed between 2005 and 2015 with t(11;14) identified on FISH performed within six months (mos) of diagnosis, and with treatment details available and if alive, a minimum of 12 mos of follow up, were enrolled. Results: The current analysis includes 848 pts with a median age of 64.4 years; 60.0% are male. The median follow-up from diagnosis for the entire cohort was 45.7 mos; 84.7% of the pts were alive at the last follow up. ISS stage distribution included: Stage 1 (35.3%), Stage II (38.9%) and stage III (25.8%). The distribution of FISH abnormalities included: del 13q (14.5%), 1q amp (12.1%), del 17p or monosomy 17 (6.1%). Pts received initial therapy with different regimens: IMiD-24.3%, PI-41.0%, both-20.8% and 13.8% had no novel agent. The drug classes by line of therapy are shown in table. An early stem cell transplant (SCT) was used in 40.8% of pts. The median time to next treatment (TTNT) after initial treatment was 15.0 (95% CI: 12.2 to 17.7) mos. The median overall survival from diagnosis for the entire cohort was 82.5 (95% CI: 73.5 to 95.8) mos. Conclusions: This is the first study to examine the outcomes of a large group of myeloma pts with t(11;14) abnormality. Pts receiving a combination if a PI and an IMiD appear to have the best survival outcomes and thse receiving an early SCT appear to have excellent survival with median OS approaching 10 years. Additional pts are being accrued to this study and additional analysis examining the variables affecting response duration and survival will be presented. [Table: see text]

scholarly journals Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8096-8096 ◽  
Author(s):  
Geetika Srivastava ◽  
Vishal Rana ◽  
Martha Lacy ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Entire Cohort ◽  
Dexamethasone Therapy

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

scholarly journals Immunotherapy in Multiple Myeloma: Experience of the Multiple Myeloma Gimema Lazio Group

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5634-5634
Author(s):  
Federico Vozella ◽  
Agostina Siniscalchi ◽  
Manuela Rizzo ◽  
Tommaso Za ◽  
Giusy Antolino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Option ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Response Duration ◽  
Advisory Board ◽  
Cell Transplant ◽  
Line Of Therapy ◽  
Almost All

Abstract Introduction .Treatment of multiple myeloma (MM) patients (pts) has radically changed over the last years following the introduction of next generation proteasome inhibitors (PI) and immunomodulatory derivatives (IMiDs). Despite the improvement of pts' outcome due to these drugs, MM remainsan incurable disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment. Almost all pts eventually relapse despite their responses to PI, IMiDs or both. Recently, one further therapeutic option for MM patients is represented bydaratumumab, an anti-CD38 monoclonal antibody approved alsofor heavily pre-treated pts who have exhausted all other therapeutic options. Patients and Methods. We report the experience of the Multiple Myeloma GIMEMA Lazio Group in 50 relapsed/refractory MM pts treated with daratumumab as monotherapy. Twenty-nine pts (58%) were men and 21 (32%) women. According to the ISS,24 pts (48%) were ISS I, 11 (22%) ISS II, 7 (14%) ISS III and 8(16%)not evaluable. According toDurie& Salmon, 20 pts (40%) were 1 A, 2 (4%) 1 B, 12 (24%) II A, 1 (2%) II B,7 (14%) III A, 3 (6%) III B and 5 (10%) not evaluable. Isotype IgG-k was found in 21 pts (42%), IgG-λ in 13 (26%), IgA-k in 6 (12%), IgA-λ in 3 (6%), micromolecular k in 5 (10%) andmicromolecular λ in 2 (4%). Median age was 62.3 years (range, 43.1 - 85.7); 32 pts (64%) were refractory to the last line of therapy; 26 (52%) had previously received a stem cell transplant (13 single autologous, 12 tandem autologous and one an autologous followed by an allogeneic transplant). After a median follow-up from diagnosis of 54.5 months (range 1.0 - 203.0) and a median of 3 previous lines of therapy (range 2 - 8), pts received a median of 3 cycles (range 1 - 23) of daratumumab. Results.Forty-seven pts (94%) performed at least one cycle and were evaluable for response. The overall response rate was 74%; in particular, 2 pts obtained a CR (4.2%), 3 pts a VGPR (6.3%), 17 pts a PR (36.2%) and 15 pts a SD (32%), while 10 pts (21.3%) presented a PD. After a median follow-up of 5.3 months (range 1 - 31) ,24 pts(65%) were still in response and alive, one pt (5.8%) died in PR due to post-allograft GVHD and 12 (32%) experienced a PD (1 CR, 1 VGPR, 6 PR and 4 SD). Seven (19%) pts died and 30 (81%) are still alive. With regard to the 3 pts not evaluable for response, 2 died early and 1 has not yet completed the first cycle. The median time to response, duration of response, progression-free survival and overall survival were 1.5 months (range 1.0 - 6.0), 6.7 months (95% CI, 4.14 - 14.21), 5.7 months (95% CI, 3.26 - 13.75) and 22.5 months (95% CI, 11.6 - 36.1), respectively. Daratumumab was well tolerated; the most common adverse events, of any grade, were infections in 20 pts (42.0%) and anaemia in 21 pts (44.0%), which did not lead to treatment discontinuation. Infusion-related reactionswere observed in 7pts (14.8%), grade I-II (4 pts), grade III (3 pts). Conclusions.Daratumumab monotherapy is an effective strategy for heavily pre-treated and refractory pts with multiple myeloma, with a favorable safety profile. This treatment option needs to be considered for pts not eligible for combination therapy of daratumumab with bortezomib or lenalidomide, recently approved also in our country. Disclosures Vozella: Takeda Oncology; Amgen: Honoraria. Annibali:Celgene; Takeda; Amgen, Janssen Cilag: Honoraria. Caravita di Toritto:Johnson & Johnson: Other: Advisory Board, Travel and Accomodation EHA; Amgen: Other: Advisory Board; Bristol-Myers Squibb: Honoraria, Other: Travel and Accomodation EMN; Takeda: Other: Advisory Board; Celgene: Other: Advisory Board, Travel and Accomodation ASH, Research Funding. Foà:NOVARTIS: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; AMGEN: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau. Petrucci:Takeda Oncology; Amgen; Celgene; BMS; Janssen Cilag: Honoraria, Other: Advisory Board.

Treatment patterns in patients with multiple myeloma (MM): A retrospective study using Medicare data.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19506-e19506 ◽  
Author(s):  
Peggy L. Lin ◽  
Dominick Latremouille-Viau ◽  
Medha Sasane ◽  
Patrick Gagnon-Sanschagrin ◽  
Hozefa A. Divan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell Transplant ◽  
Response Duration ◽  
Treatment Patterns ◽  
Cell Transplant ◽  
Medicare Data ◽  
Survival Table ◽  
Practice Methods

e19506 Background: MM is characterized by repeated relapses and refractoriness and is managed by successive lines of therapies (LT) each typically resulting in shorter response duration over prior LT. This study describes current MM treatment (tx) landscape in US clinical practice. Methods: Adult MM patients (pts) with continuous Medicare Part A, B, and D coverage initiated on 1st LT (1L), without stem cell transplant, were identified in the Medicare Research Identifiable Files (2012-2016). Claims for any MM tx within 60 days of the 1st tx constituted the tx regimen of an LT. End of LT was defined as a claim for a new MM tx > 60 days post LT initiation (tx augmentation or switch), discontinuation of all tx in a regimen for > 90 consecutive days, end of Medicare coverage/data or death. From 1L to 3L, overall survival (OS), LT duration (DoT), tx regimens and sequences were assessed. Results: 8374 MM pts with 1L (median [med] age = 76 years at 1L; 55% female) were analyzed. Over a med follow-up of 20 months (mos) from 1L (med 1L DoT = 5.6 mos), 2849 pts received a 2L (med 2L DoT = 5.6 mos) and 978 received a 3L (med 3L DoT = 4.7 mos). The most prominent tx regimens were bortezomib/corticosteroids (CS; VD) in 1L, and lenalidomide/CS (RD) in 2L and 3L. The most prevalent tx sequence was 1L VD, 2L RD and 3L VD. The 1- and 2-year OS rates were 81% [95% confidence interval: 81-82] and 68% [67-69] from 1L initiation, 80% [78-82] and 64% [61-66] from 2L, and 73% [69-76] and 55% [51-60] from 3L initiation, respectively. Conclusions: MM Medicare pts mainly cycle through bortezomib- or lenalidomide-based regimens in front LT; newer agents gain more usage in later LT. A better understanding of tx options and sequencing is warranted to prolong survival. [Table: see text]

Impact of prior autologous stem cell transplant (ASCT) in patients receiving bortezomib or dexamethasone for relapsed/refractory multiple myeloma in the APEX trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7546-7546
Author(s):  
D. T. Vogl ◽  
E. A. Stadtmauer ◽  
P. G. Richardson ◽  
P. Sonneveld ◽  
M. W. Schuster ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Initial Therapy ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Time To Progression ◽  
Phase 3 ◽  
Common Component ◽  
Line Of Therapy ◽  
The Impact

7546 Background: The phase 3 international APEX trial demonstrated significantly superior overall survival (OS), time to progression (TTP), and overall response rate (ORR: CR+PR, EBMT criteria) with bortezomib (VELCADE [Vc]) therapy for relapsed myeloma compared with dexamethasone (Dex). ASCT is a common component of initial therapy and may affect the outcome of salvage therapies. Methods: This analysis aimed to evaluate the impact of prior ASCT on the APEX results. TTP, OS, and ORR were analyzed by prior ASCT treatment. Results: Of 669 randomized patients, 451 (67%) had received prior ASCT (median follow-up in survivors was 21.9 months); in this group, Vc led to higher ORR compared with Dex (41% vs 18%, p < 0.001), higher CR rate (8% vs 0.5%, p < 0.001), and longer TTP and OS (see table), the latter despite crossover to Vc of >62% of patients originally assigned to Dex. A subset of 156 (23%) patients had ASCT as their only prior line of therapy (median follow-up in survivors was 20.0 months), with similar superiority of Vc compared with Dex in ORR (48% vs 29%, p = 0.004), CR rate (6% vs 2%, p > 0.05), and TTP. Among 218 (33%) patients with no prior ASCT (median follow-up in survivors was 21.7 months), Vc was also superior to Dex in ORR (32% vs 18%, p = 0.025), CR rate (4% vs 1%, p > 0.05), and TTP. Conclusions: Vc is consistently superior to Dex in ORR, CR rate, and TTP, regardless of prior ASCT status, and OS is superior in patients who had received prior ASCT. Vc is an effective therapy for myeloma relapsing after ASCT. NE = not estimable. [Table: see text] [Table: see text]

scholarly journals Detection of Double Hit and Triple Hit Cytogenetics at Relapse Identifies a Very High Risk Subset of Relapsed/Refractory Multiple Myeloma Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2706-2706
Author(s):  
Charanpreet Singh ◽  
Sreejesh Sreedharanunni ◽  
Vandana Panakkal ◽  
Aditya Jandial ◽  
Arihant Jain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Real World ◽  
Cell Transplant ◽  
Previous Exposure ◽  
Entire Cohort ◽  
Real World Setting ◽  
Double Hit ◽  
Active Disease

Abstract INTRODUCTION mSMART classifies high-risk Multiple Myeloma patients into Double Hit and Triple Hit Myeloma (DH/THM) on the basis of the number of high-risk cytogenetic abnormalities detected. While cytogenetics at diagnosis helps in the decision-making process regarding initial therapy, their role in relapsed MM is not very well studied. We aimed to study the clinical profile and outcomes of patients with DH/THM detected at relapse in a real-world setting. METHODS The case records of all relapsed multiple myeloma patients requiring active therapy between January 2018 and December 2020 were identified. All patients underwent bone marrow examination and repeat FISH cytogenetic analysis. The diagnosis of double hit and triple hit myeloma was based on mSMART classification (Presence of two or more of the following: IgH-FGFR3 translocation, IgH-MAF translocation, TP53 deletion, gain of chromosome 1q). Their case records were retrieved and information regarding baseline characteristics, therapy and outcomes was noted. RESULTS A total of 17 patients were diagnosed with DH/THM at relapse during the study period. Median age of the cohort was 59 years with almost an equal number of male and female patients (M=9; F=8). Renal failure (serum creatinine &gt;2.0mg/dl) was seen in 8 patients (47.1%), while bone lesions, anemia (Hemoglobin &lt;10gm/dl) and hypercalcemia (serum calcium &gt;12mg/dl) were seen in 12 (70.6%), 12 (70.6%) and 6 (35.3%) patients respectively. Five patients (29.4%) fulfilled the criteria for plasma cell leukemia. Twelve patients (70.6%) were in first relapse, while 3 patients were diagnosed at second relapse and 1 patient each at 3 rd and 5 th relapse respectively. All but 2 patients had received Bortezomib previously (N=15; 88.2%). Eleven patients (64.7%) had previous exposure to Lenalidomide and 8 patients (47.1%) had previous exposure to Thalidomide. Two patients had previously undergone autologous hematopoietic cell transplant. Median follow-up prior to diagnosing DH/THL was 28 months (Range- 5-89 months). All patients had gain of 1q with at least 3 copies, while 12 patients (70.6%) had 4 or more copies. The most common cytogenetic combination was IgH-FGFR3 translocation with gain of 1q which was seen in 10 patients (58.8%). This was followed by co-occurrence of TP53 deletion with gain of 1q in 5 patients (29.4%). Two patients (11.8%) had triple hit myeloma. Seven patients (41.2%) died within the first month of relapse and a further 3 patients died during the next month. Of the 10 patients who received at-least 1 cycle of therapy, 8 received triplet therapy with the combination of a proteasome inhibitor and an Immunomodulator, one patient received doublet with Lenalidomide and dexamethasone and one patient received Daratumumab based quadruplet therapy. Bortezomib based therapy was used in 5 patients and 4 patients received Carfilzomib based therapy. None of the patients underwent a 2 nd auto transplant. Two patients achieved VGPR or better with therapy. Of the 7 evaluable patients, 5 re-relapsed during follow up. The follow up of entire cohort ranged from 0 to 29 months. Sixteen patients (94.1%) died during follow up. The most common cause of death was progressive/active disease (9 patients, 56.3%) followed by a combination of active disease with sepsis (4 patients, 25%). Median OS was 1 month for the entire cohort. DISCUSSION The outcome of DH/THM at relapse is associated with an aggressive presentation and poor outcomes in the real-world setting. These patients are candidates for early aggressive or novel therapy or clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcomes of Patients with t(11;14) Multiple Myeloma: An International Myeloma Working Group Multicenter Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3066-3066
Author(s):  
Shaji K. Kumar ◽  
Jin Lu ◽  
Yang Terry Liu ◽  
Max Bittrich ◽  
Juan Du ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Multicenter Study ◽  
Research Group ◽  
Research Funding ◽  
University Research ◽  
Advisory Committees ◽  
Entire Cohort

Background: Multiple myeloma (MM) is a heterogeneous disease with varying survival outcomes depending on the presence of certain genetic abnormalities. Common abnormalities include trisomies, translocations involving the chromosome 14, and amplifications or deletions of chromosomes 1, 13, and 17. t(11;14), occurring in 15% of patients with myeloma, had been considered a standard risk abnormality, but recent data suggest inferior outcome. This is important as new therapeutic options such as the BCL-2 inhibitor venetoclax has been shown to be particularly effective in t(11;14) patients. Methods: This was a multicenter study to identify the outcomes of patients with t(11;14), using a retrospectively assembled cohort. Patients with MM diagnosed between 2005 and 2015 with t(11;14) identified on FISH performed within six months of diagnosis, and with treatment details available and if alive, a minimum of 12 months of follow up, were enrolled. Results: The current analysis includes 1216 patients; median age of 62.56 years; 58.7% male. The median follow-up from diagnosis for the entire cohort was 51.9 months; 69.1% of the patients were alive at the last follow up. ISS stage distribution included: Stage I (35.7%), Stage II (34.0%) and Stage III (15.1%), data was missing for the rest. The distribution of concurrent FISH abnormalities included: trisomies (3.5%), del 13q (13.3%), 1q amp (8.8%), and del 17p or monosomy 17 (5.8%). Initial regimen included: 27.2% had an immunomodulatory (IMiD), 45.9% had a proteasome inhibitor (PI), 17.7% had both, and 9.0% had no novel agent. The drug classes by line of therapy are shown in Table 1. An early stem cell transplant (defined as within 12 months of start of first line treatment) was used in 49.4% of patients. The median time to next treatment (TTNT) after starting initial treatment was 26.6 (95% CI: 23.9 to 29.2) months. The median overall survival (OS) from diagnosis for the entire cohort was 95.1 (95% CI: 85.9 to 105.9) months; 4-year estimates for those diagnosed from January 2005 to December 2009, and from January 2010 to December 2014 were 77.5% and 78.6%, respectively. The median OS for those with any one high risk FISH lesion (del 17p/ 1q amp) was 67.5 (55.2, 97.1) versus 101.7 (89.7, 107.3) months. Patients with early SCT (within 12 months of diagnosis) had better OS: 108.3 (103.8, 133.0) vs. 69.8 (61.5, 80.3) months. Conclusion: Patients with t(11;14) without high risk FISH abnormalities have an excellent survival. Patients receiving a PI + IMiD combination and those receiving autologous SCT as part of initial therapy had best survival. Though numbers are limited, patients in the later lines receiving newer drugs such as venetoclax and daratumumab had high response rates and durable responses. Disclosures Kumar: Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Bittrich:Celgene: Other: Travel Funding, Research Funding; Else Kröner Fresenius Foundation: Research Funding; Otsuka Pharmaceuticals Europe: Other: N/A; SANOFI Aventis: Membership on an entity's Board of Directors or advisory committees, N/A, Research Funding; University Hospital Wuerzburg: Employment; Bristol Myers Squibb: Research Funding; Pfizer: Other: Travel Funding; AMGEN: Other: Travel Funding; JAZZ Pharmaceuticals: Other: Travel Funding; Wilhelm Sander Foundation: Research Funding; German Research Foundation (DFG): Other: N/A; University of Würzburg: Other: N/A. Goldschmidt:Mundipharma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; John-Hopkins University: Research Funding; Dietmar-Hopp-Stiftung: Research Funding; Janssen: Consultancy, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; John-Hopkins University: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Reece:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; EDO: Membership on an entity's Board of Directors or advisory committees. Ludwig:Celgene: Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; PharmaMar: Consultancy; Janssen: Speakers Bureau; BMS: Speakers Bureau. Mangiacavalli:celgene: Consultancy; Amgen: Consultancy; Janssen cilag: Consultancy. Dimopoulos:Sanofi Oncology: Research Funding. Kastritis:Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria. Yee:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Karyopharm: Consultancy; Adaptive: Consultancy. Raje:Amgen Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Rosta:Cornerstone Research Group: Employment. Haltner:Cornerstone Research Group: Employment. Cameron:Cornerstone Research Group: Employment, Equity Ownership. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

scholarly journals Updates in the Treatment of Multiple Myeloma

2021 ◽  
Vol 19 (5.5) ◽  
pp. 648-651
Author(s):  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Standard Of Care ◽  
Initial Therapy ◽  
New Drugs ◽  
Cell Transplant ◽  
Nccn Guidelines ◽  
Drug Classes ◽  
High Risk Disease ◽  
Drug Induction ◽  
Relapsed Disease

The treatment of multiple myeloma is marked by many recent advances, but for newly diagnosed patients the standard of care for induction remains the combination of a proteasome inhibitor, immunomodulatory drug, and dexamethasone. The role of a 4-drug induction regimen is still being defined, but can be considered for patients with high-risk disease. For patients who are eligible to undergo stem cell transplant, this approach remains the preferred option, but transplant can be delayed until relapse if patients prefer. In those who are not eligible for transplant, based on impressive data with daratumumab/lenalidomide/dexamethasone, this triplet should be considered as initial therapy. In patients with relapsed disease, it is important to switch treatment to new drug classes; for this, multiple combinations can be recommended. Updated guidelines now include new drugs for refractory disease: selinexor and belantamab mafodotin, both listed as “other regimens” in the NCCN Guidelines, can be considered.

scholarly journals Treatment Patterns and Healthcare Costs Among Multiple Myeloma Patients Who Maintain Longer First Line of Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5934-5934
Author(s):  
Eric M Maiese ◽  
Terra Slaton ◽  
Chris M Kozma
Keyword(s):  
Multiple Myeloma ◽  
Healthcare Costs ◽  
Treatment Algorithm ◽  
Patient Characteristics ◽  
Initial Therapy ◽  
Treatment Patterns ◽  
Cell Transplant ◽  
First Line ◽  
Chi Square ◽  
Line Of Therapy

Abstract Introduction: The goal of multiple myeloma (MM) treatment is to control disease, prolong survival and improve quality of life (Colson 2015). One piece of evidence that a therapy is working well is the ability to maintain therapy without change. The purpose of this analysis was to describe treatment patterns and costs among MM patients who maintain first line of therapy (LOT) for at least six months. Results of this analysis will provide clinicians and payers with information about factors associated with faster progression through treatment. Methods:A US claims database (Truven Health MarketScan®) was used to identify adult patients with ≥2 MM diagnoses (ICD-9 203.0x) between Jan 1, 2005-Dec 31, 2014 (end of study) with; 1) MM treatment between Jan 1, 2007-Jun 30, 2014 and within 90 days of an MM diagnosis code (date of first MM treatment set as index date); 2) continuous medical insurance 24 months pre and ≥6 months postindex). Patients were excluded if they had 1) MM treatment preindex; 2) non-MM chemo; 3) stem cell transplant, pregnancy or HIV diagnoses. An algorithm was used to identify LOTs based on treatment gaps, changes in therapy and refractory status. Patient characteristics, treatment patterns and costs were assessed for patients without a new LOT within 6 months of starting their first LOT and for patients with a new LOT within 6 months of starting their first LOT. Treated days was defined as the time between the first day of treatment in the LOT until the last day a treatment was available based on the dispensing dates and days supplies. Categorical and continuous measures were tested with Chi-Square tests or independent t-tests, respectively. Differences in costs were tested in a general linear model with a gamma distribution and a log link. Results: Of the 2,936 patients included, 74.7% maintained LOT 1 for at least 6 months (i.e., did not have a LOT 2 within 6 months of starting their LOT 1). The average age of patients who maintained LOT 1 was 71.3 (SD 10.8) years and 56.3% were male. The average age of patients with an LOT 2 (i.e. started LOT 2 within 6 months of starting their LOT 1) was 69.7 (SD 11.0) years and 57.3% were male. Fewer patients without an LOT 2 had Commercial insurance compared to the group with an LOT 2 (25.8% vs. 29.5%). Patients without a LOT 2 were more likely to have had a lenalidomide-based (no PI) regimen for LOT 1 than patients who had an LOT 2 (35.8% vs. 22.3%; p<0.0001) Mean total costs were lower among patients without a LOT 2 compared to patients with a LOT 2 ($211,115 vs. $242,177; p<0.0001). Most of the cost difference was driven by outpatient costs, which were $90,906 for patients without an LOT 2 and $119,221 for the group with an LOT 2 (p<0.0001). The average number of treated days among patients without an LOT 2 was 143.1 days out of the possible 180 days of observation compared to 133.9 days among patients with a LOT 2 (p<0.0001). Among patients with a second LOT, based on the treatment algorithm, the observed reasons for initiating the second LOT included, 51.1% had a change in therapy with <60 day gap in therapy, 24.8% were refractory to an initial proteasome inhibitor (PI) or immunomodulatory (IMiD) therapy, 12.0% had ≥60-day gap in all therapy with a restart of the same drug and 12.1% had some other combination of reasons (i.e., change, restart of the same drug after a 60-day gap and/or 60-day gap in all therapy). Cost per day using the number of days between the start of the LOT and the end of treatment during the LOT were lowest among patients who did not progress to a second LOT during the first 180 days ($1,475/treated day). This was followed by patients who had a change in therapy alone ($1,704), those who were refractory to the initial therapy ($1,912), those who restarted after a 90-day gap with no therapy and ($1,999), and those with a combination of reasons for initiating the second LOT ($2,082). Conclusions:During the first 6-months after initiation of first LOT, approximately 75% of patients maintained LOT 1. Patients who maintained LOT 1 tended to be older, have lower costs, more treated days, and more frequently treated with lenalidomide-based (no PI) regimens at LOT 1. This analysis suggests that maintaining lines of therapy longer is associated with reduced healthcare costs and using a lenalidomide-based regimen in LOT 1 may be associated with longer time to next therapy, which may be helpful when considering treatment sequencing. Disclosures Maiese: Janssen Scientific Affairs, LLC: Employment. Slaton:CK Consulting Associates, LLC: Employment. Kozma:CK Consulting Associates, LLC: Employment.

Evolving Unmet Need in Patients Refractory to Lenalidomide: Overview of the Clinical Trials in Relapsed/Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Maria-Victoria Mateos ◽  
Rohan Medhekar ◽  
Istvan Majer ◽  
Mehmet Turgut
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Literature Review ◽  
Board Of Directors ◽  
Unmet Need ◽  
Publicly Traded ◽  
First Line ◽  
Advisory Committees ◽  
Line Of Therapy

Introduction: The majority of newly diagnosed multiple myeloma (NDMM) patients are currently treated with lenalidomide-based regimens as their first line of therapy. This trend is likely to continue in the coming years. Typically, lenalidomide is administered until disease progression and has significantly contributed to better outcomes in these patients. However, most patients relapse, and prognosis worsens with each relapse. The choice of optimal treatment for patients who relapse while receiving lenalidomide as first line of therapy is unclear. Moreau et al (Blood Cancer J. 9, 38 [2019]) concluded that there is limited data on approved combinations for treating these patients and are restricted by the low number of lenalidomide-refractory patients enrolled in the pivotal trials. Results from the ongoing clinical trials of the combination of carfilzomib and anti-CD38 antibodies were not available at the time of the Moreau et al publication. The aim of this targeted literature review was to include this new data and to summarize currently available evidence on progression-free survival (PFS) for the treatment of RRMM patients who progressed on lenalidomide-based regimens. Methods: A targeted literature review was conducted to identify registrational clinical trials in patients with RRMM reporting PFS outcomes. PubMed, congress proceedings, and product labels were searched between Jan 2014 to July 2020. In addition to PFS, demographic, disease characteristics and treatment history were extracted for the trial populations to contextualize potential variations in study outcomes. The regimens studied in these trials were classified as lenalidomide-based, proteasome inhibitor (PI)-based and pomalidomide-based. Number of prior lines of therapy, prior exposure and refractoriness to lenalidomide and bortezomib were reported. Results: Twelve registrational trials were identified based on the search criteria (Table 1). Most pivotal trials assessing lenalidomide-based regimens (POLLUX, ELOQUENT-II, TOURMALINE-MM1) except the ASPIRE trial excluded patients who were refractory to lenalidomide. Trials evaluating PI-based regimens (e.g., CANDOR) or pomalidomide-based regimens (e.g., OPTIMISMM) included these patients, with more recent studies enrolling a larger proportion. Percentage of lenalidomide-exposed (and lenalidomide refractory) ranged from 40% (32%) in CANDOR to 98% (90%) in ELOQUENT III. These studies also enrolled a larger proportion of patients who were bortezomib-exposed, although most of these patients were at first relapse, with the exception of ELOQUENT III and ICARIA where most patients were at third relapse. Among lenalidomide-refractory patients, the median-PFS (mPFS) observed for the pomalidomide-based regimens ranged from 9.5 to 10.1 months and that observed for PI-based regimens ranged from 4.9 to 25.7 months. PFS in the lenalidomide-refractory subgroup was considerably shorter than in the ITT population. The mPFS for patients receiving carfilzomib/daratumumab/dexamethasone (KDd; CANDOR) and isatuximab/carfilzomib/dexamethasone (IsaKd; IKEMA) was not reached at median follow-up of 16.9 and 20.7 months respectively. While the mPFS for (KDd) for lenalidomide-refractory patients in CANDOR trial was not yet reached at median follow up of 16.9 months; the mPFS of 25.7 months for KDd in the MMY-1001 trial appears to be the longest among the assessed regimens. Conclusion: Patients refractory to lenalidomide have shorter PFS and represent a population with high unmet need. This targeted literature review suggests that the PI-based KDd regimen provides longer PFS compared to other lenalidomide-sparing regimens in lenalidomide-refractory populations. Heterogeneity across trial populations may limit the comparability of these treatments. Disclosures Mateos: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; GlaxoSmithKline: Consultancy. Medhekar:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Majer:Amgen (Europe) GmbH: Current Employment, Current equity holder in publicly-traded company.

scholarly journals Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

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