Practice Patterns in Newly Diagnosed Multiple Myeloma in the Prospective Observational Commpass Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4502-4502 ◽  
Author(s):  
Joshua Necamp ◽  
Sulsal Haque ◽  
Saulius K Girnius

Abstract Introduction:The management of multiple myeloma has become increasingly complex, given late age of onset, underlying co-morbidities, plethora of drugs, and variable clinical presentation and natural history. Practice patterns likely vary based on practice type, physician experience, and geographic distributions. The Multiple Myeloma Research Foundation's (MMRF) CoMMpass Trial (Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile) is a prospective, longitudinal, observation trial in NDMM with the primary goal of correlating patient data and response with molecular profiles. Here, we evaluate practice patterns in NDMM the CoMMpass Trial based on staging, high-risk features, and demographics. Methods: Clinical data were derived from MMRF's CoMMpass IA8, accessed in late July 2016 on https://research.themmrf.org/rp/explore. Independent categorical variables analyzed include International Staging System (ISS), Revised-ISS (R-ISS), LDH (normal vs. above upper limit of normal), Fluorescence-In-Situ Hybridization (FISH) (standard vs. high risk (t(4;14), t(14;16), t(14:20), del17p)), race, performance status (PS) (0-1, 2, 3-4), age (>65, 65-75, 76-80, >80 years), and gender. Dependent variables include use of doublets vs. triplets, the use of triplets using combined immunomodulatory/proteosome inhibition (IMID/PI), receiving or not receiving an autologous stem cell transplantation (ASCT), and timing of transplant (<10 vs. >10 months). For high-risk MM, defined as ISS 3, R-ISS 3, elevated LDH, or high risk FISH, patients receiving doublet therapy without an autologous stem cell transplantation were further analyzed for performance status and age. Descriptive statistics were used. Chi-square testing was used to compare variables, using STATA v14.1. Results: Data on 921 patients has been released and was reviewed. Although men and women had similar upfront therapy, including the use of triplet (57% vs. 61%, p=0.483) and IMID/PI combinations (56% vs. 62%, p=0.181), women were more likely to have an ASCT (44% vs. 34%, p=0.002). When compared to European Americans (EA), African-Americans (AA) were less likely to receive triplets (47% vs. 61%, p=0.004), IMID/PI combination (55% vs. 59%, p=0.001), and ASCT (30% vs. 40%, p=0.034). Patients with high-risk disease were not more likely to be treated more aggressively. Patients with ISS Stage 3 disease were less likely to receive triplets (50% vs. 64%, p=0.002), IMID/PI combinations (51% vs. 66%, p=0.001), or an ASCT (26% vs. 48%, p=<10-3). When comparing standard-risk MM, as defined by LDH or FISH, high-risk patients were not more likely to receive triplet therapy or ASCT. Performance status did not correlate triplet use, but lower rates of IMID/PI combinations and ASCT were noted in those with worse PS. We subsequently reviewed patients with high-risk features who were treated with doublet therapy and without ASCT, specifically looking performance status and age. Of those with elevated LDH, 12 (46%) were younger than 65 years and 12 (46%) had PS<1. Of those with high risk FISH, 20 (49%) were younger than 65 years and 37 (76%) had PS<1. Of those with ISS 3, 24 (26%) were younger than 65 years and 49 (56%) had PS<1. Of those with R-ISS 3, 12 (44%) were younger than 65 years and 17 (63%) had PS<1. Conclusions: The MMRF CoMMpass trial allowed assessment of practice patterns in the United States both inside and outside of academic medical centers. AA appear to be treated less aggressively, possibly explaining shorter survival despite more favorable cytogenetics. Second, high-risk disease does not appear to be treated more aggressively, even in younger patients with excellent performance status. This presented data must be interpreted with caution since this trial does not capture the treating physician's decision-making, nor survival data. Disclosures Girnius: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau.

2007 ◽  
Vol 25 (17) ◽  
pp. 2434-2441 ◽  
Author(s):  
Michele Cavo ◽  
Patrizia Tosi ◽  
Elena Zamagni ◽  
Claudia Cellini ◽  
Paola Tacchetti ◽  
...  

Purpose We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM). Patients and Methods A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B). Results As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70). Conclusion In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.


Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3474-3480 ◽  
Author(s):  
Frederic Garban ◽  
Michel Attal ◽  
Mauricette Michallet ◽  
Cyrille Hulin ◽  
Jean H. Bourhis ◽  
...  

The Intergroupe Francophone du Myélome (IFM) initiated 2 trials in 1999 to study patients with high-risk (β2-microglobulin level greater than 3 mg/L and chromosome 13 deletion at diagnosis) de novo multiple myeloma. In both protocols, the induction regimen consisted of vincristine, doxorubicin, and dexamethasone (VAD) followed by first autologous stem cell transplantation (ASCT) prepared by melphalan 200 mg/m2. Patients with an HLA-identical sibling donor were subsequently treated with dose-reduced allogeneic stem cell transplantation (IFM99-03 trial), and patients without an HLA-identical sibling donor were randomly assigned to undergo second ASCT prepared by melphalan 220 mg/m2 and 160 mg dexamethasone with or without anti–IL-6 monoclonal antibody (IFM99-04 protocol). Two hundred eighty-four patients—65 in the IFM99-03 trial and 219 in the IFM99-04 trial—were prospectively treated and received at least one course of VAD. On an intent-to-treat basis, overall survival (OS) and event-free survival (EFS) did not differ significantly in the studies (medians 35 and 25 months in the IFM99-03 trial vs 41 and 30 months in the IFM99-04 trial, respectively). With a median follow-up time of 24 months, the EFS of the 166 patients randomly assigned in the tandem ASCT protocol was similar to the EFS of the 46 patients who underwent the entire IFM99-03 program (median, 35 vs 31.7 months), with a trend for a better OS in patients treated with tandem ASCT (median, 47.2 vs 35 months; P = .07). In patients with high-risk de novo MM, the combination of ASCT followed by dose-reduced allogeneic transplantation was not superior to tandem dose–intensified, melphalan-based ASCT.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3000-3000 ◽  
Author(s):  
Aleksandr Lazaryan ◽  
Hien Duong ◽  
Lisa Rybicki ◽  
Frederic J. Reu ◽  
Robert Dean ◽  
...  

Abstract Abstract 3000 Autologous stem cell transplantation (ASCT) remains the standard upfront therapy of younger patients with multiple myeloma (MM). Identifying a prognostic threshold amount of mobilized CD34+ hematopoietic stem cells (SC) may become an important modifiable parameter in the era of novel stem cell mobilization strategies. While poor mobilization of CD34+ cells has been shown to cause delays in hematopoietic recovery, the data on long-term clinical outcomes of patients with inferior CD34+ SC collection (‘under mobilizers’) are limited. We analyzed prospectively collected data on 239 adult patients with MM who underwent ASCT at our institution from 01/1996 to 12/2009. Fifty-one patients (21.3%) who collected less than 4 × 106/kg CD34+ SC were classified as ‘under mobilizers’ and were compared to the rest of the study population (n=188) who collected ≥ 4 × 106/kg CD34+ SC. Even though under mobilizers were slightly older (median 59 vs. 54 years, p =0.01), had longer time from diagnosis to ASCT (11 vs. 8 months, p =0.05), and required more days of leukapheresis (5 vs. 3 days, p <0.001), they did not differ from the other group according to the number of prior treatment regimens, mobilization method (only 2 patients received plerixafor), performance status, or disease remission status at transplant (all p >0.2). Median time-to-recovery for both neutrophils (11 vs. 10 days, p <0.001) and platelets (13 vs. 12 days, p <0.001) was delayed among under mobilizers. Under mobilizers had worse relapse-free survival (RFS) (hazard ratio [HR]=1.49, 95% CI, 1.03–2.16, p =0.03) and non-relapse mortality (NRM) (HR=3.59, 95% CI, 1.51–8.56, p <0.01) in multivariable Cox proportional hazards analysis. Even though the association between poor CD34+ SC collection and inferior overall survival did not reach statistical significance (HR=1.42, 95% CI, 0.94–2.16, p =0.1), under mobilizers were found to have significantly higher rates of 100-day post-transplant mortality (p =0.02). We conclude that in the context of ASCT for MM, failure to collect ≥ 4 × 106/kg CD34+ SC is independently associated with worse RFS and NRM. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 38 (34) ◽  
pp. 4030-4041
Author(s):  
Meletios A. Dimopoulos ◽  
Ivan Špička ◽  
Hang Quach ◽  
Albert Oriol ◽  
Roman Hájek ◽  
...  

PURPOSE Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed. PATIENTS AND METHODS The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization. RESULTS Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%. CONCLUSION Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8021-8021
Author(s):  
Adriana C. Rossi ◽  
Jorge Monge ◽  
Ruben Niesvizky ◽  
Jing Mei Hsu ◽  
Tsiporah Shore ◽  
...  

8021 Background: Autologous stem cell transplantation (ASCT) remains a standard of care of eligible patients with multiple myeloma, despite the many novel therapies introduced over the past decade. High dose melphalan (HDM) is the only approved regimen to date. Lenalidomide (LEN) is an oral immunomodulatory drug which has become the backbone of myeloma therapy from induction through salvage and maintenance. Early studies noted a dose response relationship, and found myelosuppression to be the dose limiting toxicity. We previously reported on our phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT, where no DLT was noted up to 350mg PO daily of LEN. Here we report the phase 2 data of patients undergoing ASCT with combination conditioning regimen. Methods: 50 patients with relapsed/refractory multiple myeloma (RRMM) underwent ASCT using HDLEN+HDM conditioning. HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. TPatients were heavily pre-treated: 32% had prior HDM-ASCT, 96% had received prior lenalidomide, and 42% prior pomalidomide; 40% prior anti-CD38 mAB. Of note, 68% entered the study with progressive disease at time of enrollment. Results: Overall response rate was 96%, with 80% being ≥VGPR. Median progression free survival (PFS) was noted at 14.3 months, while overall survival (OS) was 68.2 months. PFS was similar when patients were stratified by prior ASCT, depth of response at enrollment, or presence of high risk FISH. Toxicities were mostly hematologic (100% neutropenia and thrombocytopenia, 90% anemia), GI (88% diarrhea, 72% nausea, 42% vomiting) and metabolic (30-96% derangement in electrolytes), and similar to historical controls receiving HDM alone. Second malignancies were noted in 2 patients. Conclusions: HDLEN/HDM is a well tolerated and effective conditioning regimen for ASCT in patients with RRMM. This regimen merits further investigation as ASCT is likely to remain an integral part of the treatment of RRMM patients, yet few advancements have been made to this modality. HDLEN may be particularly useful in patients with high risk disease and those progressing after multiple lines of therapy. HDLEN added little toxicity to HDM and SPMs were not more frequent than expected per SEER database for patients in this age range. Clinical trial information: NCT01054196. [Table: see text]


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5329-5329
Author(s):  
Gregory Franz ◽  
Brian McClune ◽  
Francis Buadi ◽  
William Walsh ◽  
Frank White ◽  
...  

Abstract Autologous stem cell transplantation (ASCT) increases the overall survival of patients with newly diagnosed multiple myeloma (MM), and it has become standard of care in this setting. Long-term survivors of ASCT transplanted for lymphoma or Hodgkin’s disease are known to have a high risk of developing myelodysplasia (MDS), but the risk of MDS is not clear for patients transplanted for MM. From 1996 through 2005, 82 patients underwent ASCT for MM at our center, survived at least 6 months and have adequate documentation of follow-up for review. The group included 47 males and 35 females of median age 56 years (range, 37–74 yrs). Median time from diagnosis to ASCT was 8.2 mos (range, 2.6–86.1 mos). Prior to coming to transplantation, 28% had received melphalan (MEL), 98% received some form of chemotherapy, and 34% received radiation. This prior therapy included 1 or 2 regimens for 48% of the patients, and more than 2 regimens for 52% of patients. Mobilization was effected using CYC plus growth factor for 79% of the patients, CAD or VAD plus growth factor for 17%, and growth factor alone for 4%. The median mobilization rate was 28.7 × 106 CD34/L blood processed (range, 2.0–250.1 × 106 CD34/L blood processed). A single ASCT was provided for 68%, and 32% underwent ASCT more than once. High-dose MEL alone was used as the preparative regimen for 83%, and the remainder received at least one ASCT with a more intensive preparative regimen. The median CD34 dose for the first ASCT was 5.1 × 106/kg (range, 0.4–113.0 × 106/kg). Nine patients developed MDS. The 5-yr actuarial risk was 26% (95% CI, 8–43%). On multivariate analysis, there was a trend for an increased risk of developing MDS with a CD34 cell dose <3 × 106/kg (HR 3.0, 95% CI 1.0–16.2, p=0.059), but there were otherwise no significant prognostic factors. Eight of the 9 patients with MDS had a PR or better as the best response to ASCT for MM. Five of the MDS patients had relapse of MM as well. Median survival after the diagnosis of MDS was 18.1 mos. Five patients with MDS have died, two from recurrent myeloma, two from AML, and one from sepsis and MDS. The median survival for all patients was 51.7 mos from ASCT and 69.1 mos from diagnosis, and there were no differences in survivals between those with or without MDS. We conclude that there is a relatively high risk of MDS after ASCT for MM, but development of MDS does not appear to worsen overall survival.


2018 ◽  
Vol 139 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Tsuyoshi Muta ◽  
Toshihiro Miyamoto ◽  
Tomohiko Kamimura ◽  
Yoshinobu Kanda ◽  
Masaharu Nohgawa ◽  
...  

Autologous stem cell transplantation (ASCT) has been employed for patients with relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective study aimed to examine the survival benefit from salvage ASCT. Among 446 patients with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT, the employment of which reduced the risk of mortality after relapse (p = 0.041). Using the parameters before initial ASCT, the advantage of salvage ASCT compared to standard therapy was confirmed in the subgroup with an international staging system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also confirmed in the subgroup excluding those with early relapse within 7 months after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a favorable prognosis is apparent for those with a time to relapse after initial ASCT of longer than 24 months. The overall survival after salvage ASCT was favorable excluding patients with the following factors: early relapse, poor PS, moderate/severe renal comorbidity, and progressive disease (p < 0.001). In conclusion, our results reinforced the evidence for encouraging salvage ASCT for eligible patients.


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