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.

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 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.

Immunologic Recovery after Autologous Transplant in Multiple Myeloma and Progression Free Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4444-4444
Author(s):  
Fernanda Maria Rodrigues Trigo-Miranda ◽  
Rui Cordeiro Bergantim ◽  
Ricardo Moreira Pinto ◽  
Patricia Guimarães ◽  
Jose E. Guimaraes
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Cell Transplant ◽  
Haematopoietic Progenitor Cell ◽  
Free Survival ◽  
Post Transplant ◽  
Historical Comparison ◽  
Significant Difference

Abstract Several factors influencing disease progression and survival have been identified in multiple myeloma (MM). We analysed a series of 49 consecutive patients with MM that underwent autologous haematopoietic progenitor cell transplant (HPCT) in one center regarding the following variables: use of G-CSF for haematopoietic recovery post-transplant; recovery of normal IgM levels at day +100 post-transplant; levels of lymphocytes namely of the CD4+ and CD8+ subsets also at day +100. Before 2006, all patients had G-CSF starting 24 hours after the cell infusion until neutrophil &gt; 500×10^9/L in two consecutive days; in the years 2006–2008, no G-CSF was given to transplanted patients. A historical comparison was done and at the time of this study no significant difference in progression free survival (Kaplan-Meyer analysis), was detected between the two groups, possibly due to the shorter follow-up of the “no G-CSF” (n=19) group; nevertheless median progression free survival (PFS) in the “G-CSF” group was 12 months while median PFS was not attained in the “no G-CSF” group (median follow-up = 7 months). Post transplant IgM levels were also determined in 39 patients. Eighteen patients recovered normal IgM levels at day +100 (46.8 %) and 21 (53.8 %) did not. Comparison of Kaplan-Meyer curves for the two groups did not show any statistically significant difference but there is a sharp difference between median PFS of the “low IgM” (10 months) and the “normal IgM” (27 months) groups. CD4/CD8 ratio was determined in 18 patients at day +100. The ratio varied between 0 and 0.63 (median – 0.305). No correlation was found between post-transplant IgM recovery and CD4/CD8 ratio. In conclusion, in our series of MM patients treated with autologous HPCT we could not find a definite relationship between immunologic recovery and response to treatment although there is a trend to a better outlook of the patients which recover normal IgM levels. It is also uncertain whether use of G-CSF in the post-transplant period would have any effect on disease behaviour.

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

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]

Autologous stem cell transplantation versus no transplant in patients above 70 with multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20509-e20509
Author(s):  
Christopher Lemieux ◽  
Lori S. Muffly ◽  
David Joseph Iberri ◽  
Andrew Rezvani ◽  
Robert Lowsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival ◽  
First Line Therapy ◽  
Included Patient

e20509 Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m2 (75%, n = 40) and 140 mg/m2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients < 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]

scholarly journals The evolution of stem-cell transplantation in multiple myeloma

2018 ◽  
Vol 9 (5) ◽  
pp. 123-133 ◽  
Author(s):  
Sarakshi Mahajan ◽  
Nidhi Tandon ◽  
Shaji Kumar
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cell Transplant ◽  
First Relapse

Autologous stem-cell transplantation (ASCT) remains an integral part of treatment for previously untreated, and may have value in the treatment of relapsed patients with, multiple myeloma (MM). The addition of novel agents like immunomodulators and proteasome inhibitors as induction therapy before and as consolidation/maintenance therapy after ASCT has led to an improvement in complete response (CR) rates, progression-free survival (PFS) and overall survival (OS). With advances in supportive care, older patients and patients with renal insufficiency are now able to safely undergo the procedure. The data concerning the timing of ASCT (early in the disease course or at first relapse), single versus tandem (double) ASCT and the role and duration of consolidation and maintenance therapy post ASCT remain conflicting. This review aims to discuss the evolution of stem-cell transplant over the past 3 decades and its current role in the context of newer, safer and more effective therapeutic agents.

Very Good Partial Response and Complete Response Predict Superior Overall Survival and Progression Free Survival After Single Autologous Stem Cell Transplant in Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4111-4111
Author(s):  
Victor H Jimenez-Zepeda ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
Christine Chen ◽  
Andrew Winter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact

Abstract Abstract 4111 In multiple myeloma (MM), the impact of complete response (CR) and very good partial response (VGPR) achievement has been shown mostly after introduction of high dose therapy (HDT) supported by autologous stem cell transplant (ASCT). Recently, the IFM group reported the impact of achievement of CR and VGPR in double ASCT. The purpose of this study is to confirm the prognostic value of CR/VGPR in a large group of patients treated with single ASCT. Methods All consecutive patients who underwent single ASCT at Princess Margaret Hospital between January 2000 and December 2007 were evaluated. Patients were mobilized with cyclophosphamide and G-CSF and majority were conditioned with melphalan 200mg/m2. Response to therapy was assessed according to the IMWC including VGPR. Progression Free Survival (PFS) and Overall Survival (OS) were measured from transplant date to the date of death or last follow-up. OS and DFS were analyzed using the Kaplan-Meier Method. The Cox proportional hazard model was used to assess CR and VGPR and some other prognostic markers at presentation such as age, B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP> 20mg/L, albumin<35g/L and creatinine > 200 μmol/L. All p-values were 2-sided and statistically significant if <0.05. Results 788 patients were identified for the study; their median age was 56 years (30–73). Patient's characteristics are listed in Table 1. Response was assessed at day 100 after ASCT and showed a CR of 6%, PR of 37.5%, and VGPR of 53% (Overall Response rate of 95.5%). Median OS and PFS for the group were 77.43 months and 20.63 months respectively. The median OS and PFS were significantly better for patients who achieved CR/VGPR, 104.5 months versus 51.7 months, and 26.3 months versus 13.53 months respectively. With a median follow-up of 44 months there is no significant difference in OS for those patients who achieved VGPR/CR after induction therapy with novel agents. However, PFS is better in those patients receiving novel agents who achieved VGPR/CR (Median PFS of 24.63months versus 12.4 months respectively (p=0.01). Multivariate analysis shows CR/VGPR as an independent prognostic factor for OS and PFS (Fig 1 and 2). B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP > 20mg/L, albumin<35g/L and creatinine > 200 μmol/L failed to be important factor for survival in the multivariate analysis. Our data suggests that VGPR/CR is clearly important in the pre-novel agents era and for the smaller group of patients who had novel agents induction there is a benefit in PFS and with a longer follow-up perhaps in OS. In conclusion, VGPR/CR remains a simple and powerful indicator in the context of single ASCT and should be considered a relevant objective for MM treatment. Table 1. Clinical characteristics of patients with Multiple Myeloma undergoing single ASCT Clinical characteristic N=788 Median Range % Age (years) 58 31–74 Male 59.4% Female 40.6% Hemoglobin (g/L) 114 54–180 Creatinine (μmol/L) 107 28–1409 B2-microglobulin ((μmol/L) (N=718) 508 260–7270 Albumin (g/L) (N=650) 38 23–54 IgG 51.1% IgA 31.3% IgM 0.4% IgD 0.7% Biclonal 9.9% Not Detected 6.6 Kappa 59.4% Lambda 32.9% Biclonal 2% Not Detected 5.7% Calcium (μmol/L) 2.29 1.62–4.66 LDH (IU/L) (N=754) 235 50–1470 Induction Treatment: 52.2% VAD 22.8% Dexamethasone 6.3% TD 2.3% CP 3.8% DPACE/DTPACE 1.7% DVD 8% CyBORD 2% VD Ab: VAD: Vincristine, Adriamycin and dexamethasone, TD: Thalidomide and Dexamethasone; CP: Cyclophosphamide and Prednisone, DVD: Doxil, Velcade and Dexamethasone, CyBORD: Cyclophosphamide, Bortezomib and Dexamethasone and VD: Valcade and Dexamethasone Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

scholarly journals Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

2020 ◽  
Vol 10 (11) ◽  
Author(s):  
Jonathan L. Kaufman ◽  
Meletios A. Dimopoulos ◽  
Darrell White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Subgroup Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Poor Outcomes ◽  
Line Of Therapy

Abstract High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk.

scholarly journals Bendamustine-Based Regimens as Salvage Therapy in Refractory/Relapsed Multiple Myeloma Patients: A Retrospective Real-Life Analysis by the Polish Myeloma Group

2021 ◽  
Vol 10 (23) ◽  
pp. 5504
Author(s):  
Norbert Grzasko ◽  
Grzegorz Charlinski ◽  
Marta Morawska ◽  
Pawel Kicinski ◽  
Anna Waszczuk-Gajda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Real Life ◽  
Progression Free Survival ◽  
Study Groups ◽  
Cell Transplant ◽  
Incurable Disease ◽  
Drug Regimens ◽  
Previously Treated ◽  
Additional Agent

Multiple myeloma (MM) is an incurable disease and patients become refractory to the treatment in the course of the disease. Bendamustine-based regimens containing steroids and other agents are among the therapeutic options offered to MM patients. Here, we investigated the safety and the efficacy of bendamustine used in patients with refractory/relapsed MM (RRMM). The patients were treated with bendamustine and steroids (n = 52) or bendamustine, steroids and immunomodulatory agents or proteasome inhibitors (n = 53). Response rates, progression-free survival (PFS), overall survival (OS) and frequency of adverse events were compared between both study groups. Most efficacy measurements were better in patients treated with three-drug regimens: overall response rate (55% versus 37%, p = 0.062), median PFS (9 months versus 4 months, p < 0.001), median OS survival (18 months versus 12 months, p = 0.679). The benefit from combining bendamustine and steroids with an additional agent was found in subgroups previously treated with both lenalidmide and bortezomib, with stem cell transplant and with more than two previous therapy lines. Toxicity was similar in both study groups and bendamustine-based therapies were generally well-tolerated. Our study suggests that bendamustine may be an effective treatment for patients with RRMM. Three-drug regimens containing bendamustine, steroids and novel agents produced better outcomes and had acceptable toxicity. The efficacy of bendamustine combined with steroids was limited.

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