OAB-052: Impact of chromosome 1 abnormalities on newly diagnosed multiple myeloma treated with proteasome inhibitor, immunomodulatory drug, and dexamethasone: analysis from the ENDURANCE ECOG-ACRIN E1A11 trial

Aim: To describe treatment patterns and outcomes in nontransplant newly diagnosed multiple myeloma (NDMM) patients in Spain. Methods: This retrospective study included two cohorts of NDMM patients diagnosed between 1 January 2012 to 31 December 2013 and 1 April 2016 to 31 March 2017. Results: Among 113 patients, proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%) were the most common first-line (1L) therapies. Use of PI + immunomodulatory drug-based regimens increased between the cohorts; PI-based regimens without an alkylator/immunomodulatory drug decreased. Use of 1L oral regimens was low but increased over time; use of maintenance therapy was low across both periods. Median 1L duration of treatment was 6.9 months. Conclusion: Short 1L duration of treatment and low use of 1L oral regimens and maintenance therapy highlight unmet needs in NDMM.

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Patients with newly diagnosed multiple myeloma and chromosome 1 amplification have poor outcomes despite the use of novel triplet regimens

American Journal of Hematology ◽

10.1002/ajh.23705 ◽

2014 ◽

Vol 89 (6) ◽

pp. 616-620 ◽

Cited By ~ 12

Author(s):

Noa Biran ◽

Jyoti Malhotra ◽

Emilia Bagiella ◽

Hearn Jay Cho ◽

Sundar Jagannath ◽

...

Keyword(s):

Multiple Myeloma ◽

Chromosome 1 ◽

Newly Diagnosed ◽

Poor Outcomes

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Immunomodulatory drug- and proteasome inhibitor-backbone regimens in the treatment of relapsed multiple myeloma: an evidence-based review

Expert Review of Hematology ◽

10.1080/17474086.2020.1804356 ◽

2020 ◽

Vol 13 (9) ◽

pp. 943-958 ◽

Cited By ~ 3

Author(s):

Larysa Sanchez ◽

Kevin Barley ◽

Joshua Richter ◽

Joseph Franz ◽

Hearn Jay Cho ◽

...

Keyword(s):

Multiple Myeloma ◽

Proteasome Inhibitor ◽

Evidence Based ◽

Immunomodulatory Drug

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Pharmacokinetics of Daratumumab Following Intravenous Infusion in Relapsed or Refractory Multiple Myeloma (MM) after Prior Proteasome Inhibitor (PI) and Immunomodulatory Drug (IMiD) Treatment

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2015.07.564 ◽

2015 ◽

Vol 15 ◽

pp. e269-e270 ◽

Cited By ~ 2

Author(s):

P.L. Clemens ◽

X. Yan ◽

T. Puchalski ◽

H.M. Lokhorst ◽

S. Lonial ◽

...

Keyword(s):

Multiple Myeloma ◽

Intravenous Infusion ◽

Proteasome Inhibitor ◽

Refractory Multiple Myeloma ◽

Immunomodulatory Drug

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Proteasome Inhibitor or Immunomodulators Which is The Optimal Maintenance For Newly Diagnosed Multiple Myeloma: A 7-Year Real-World Data in China.

10.21203/rs.3.rs-205639/v1 ◽

2021 ◽

Author(s):

Xiaoyan Han ◽

Chunxiang Jin ◽

Gaofeng Zheng ◽

Donghua He ◽

Yi Zhao ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Maintenance Therapy ◽

Proteasome Inhibitor ◽

Consolidation Therapy ◽

Newly Diagnosed ◽

Real World Data ◽

High Risk Patients ◽

Optimal Maintenance ◽

Risk Patients

Abstract Background: According to different patients’ subgroups choose optimal maintenance therapy. Methods: 226 Newly Diagnosed Multiple Myeloma (NDMM) patients in our center were included, the patients’ characteristics, survival, response, subgroup analysis, adverse reactions were compared between the patients with or without maintenance, proteasome inhibitor (PI) or immunomodulators (IMiDs) maintenance. And the survival of different maintenance duration of bortezomib-based regimens was also analyzed.Results: The maintenance therapy not only upgraded more patients’ response (34.3 vs. 13.3%, p= 0.006), but also significantly prolonged the patients’ PFS (median PFS: 41.1 vs. 10.5 months, p < 0.001) and OS (median OS: not reached vs. 38.6 months, p < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs. 38.5 months, p = 0.034) and OS (median OS: not reached vs. 78.5 months, p = 0.041) can both benefit from bortezomib-based maintenance. The patients younger than 65 years old with bortezomib-based maintenance significantly prolonged the OS (p= 0.032). Patients achieving the only partial response (PR) after induction and consolidation therapy experienced a significantly longer PFS and OS with bortezomib-based maintenance compared to IMiDs (p= 0.007, 0.002). Besides, the high-risk patients (ISS 2-3, DS 2-3 and RISS 2-3) with bortezomib-based maintenance can benefit PFS (p= 0.002, 0.02, 0.06, respectively) and OS (p=0.059, 0.047, 0.044, respectively) compared with IMiDs. The OS was significantly prolonged in the patients who received ≥12 months of bortezomib-based maintenance than those with maintenance < 12 months (p< 0.001), but no difference was observed in OS between the patients who received the 12-24 or ≥ 24months of bortezomib-based maintenance (p= 0.292).Conclusion: Maintenance therapy can significantly improve the survival of NDMM patients. Bortezomib-based regimens maintenance was more superior to IMiDs in overall PFS and OS. The beneficial effect is most evident in patients achieving the only PR after induction and consolidation therapy, and the high-risk patients. Moreover, younger patients also could benefit from bortezomib-based maintenance in OS. The bortezomib-based maintenance duration lasting 12-24 months after induction and consolidation therapy can reach a satisfactory OS.

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Carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) as induction therapy for transplant-eligible, newly diagnosed multiple myeloma patients (Myeloma XI+): Interim analysis of an open-label randomised controlled trial

PLoS Medicine ◽

10.1371/journal.pmed.1003454 ◽

2021 ◽

Vol 18 (1) ◽

pp. e1003454

Author(s):

Graham H. Jackson ◽

Charlotte Pawlyn ◽

David A. Cairns ◽

Ruth M. de Tute ◽

Anna Hockaday ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Interim Analysis ◽

Proteasome Inhibitor ◽

Group Versus ◽

Control Group ◽

Newly Diagnosed ◽

To Receive ◽

Good Partial Response

Background Carfilzomib is a second-generation irreversible proteasome inhibitor that is efficacious in the treatment of myeloma and carries less risk of peripheral neuropathy than first-generation proteasome inhibitors, making it more amenable to combination therapy. Methods and findings The Myeloma XI+ trial recruited patients from 88 sites across the UK between 5 December 2013 and 20 April 2016. Patients with newly diagnosed multiple myeloma eligible for transplantation were randomly assigned to receive the combination carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) or a triplet of lenalidomide, dexamethasone, and cyclophosphamide (Rdc) or thalidomide, dexamethasone, and cyclophosphamide (Tdc). All patients were planned to receive an autologous stem cell transplantation (ASCT) prior to a randomisation between lenalidomide maintenance and observation. Eligible patients were aged over 18 years and had symptomatic myeloma. The co-primary endpoints for the study were progression-free survival (PFS) and overall survival (OS) for KRdc versus the Tdc/Rdc control group by intention to treat. PFS, response, and safety outcomes are reported following a planned interim analysis. The trial is registered (ISRCTN49407852) and has completed recruitment. In total, 1,056 patients (median age 61 years, range 33 to 75, 39.1% female) underwent induction randomisation to KRdc (n = 526) or control (Tdc/Rdc, n = 530). After a median follow-up of 34.5 months, KRdc was associated with a significantly longer PFS than the triplet control group (hazard ratio 0.63, 95% CI 0.51–0.76). The median PFS for patients receiving KRdc is not yet estimable, versus 36.2 months for the triplet control group (p < 0.001). Improved PFS was consistent across subgroups of patients including those with genetically high-risk disease. At the end of induction, the percentage of patients achieving at least a very good partial response was 82.3% in the KRdc group versus 58.9% in the control group (odds ratio 4.35, 95% CI 3.19–5.94, p < 0.001). Minimal residual disease negativity (cutoff 4 × 10−5 bone marrow leucocytes) was achieved in 55% of patients tested in the KRdc group at the end of induction, increasing to 75% of those tested after ASCT. The most common adverse events were haematological, with a low incidence of cardiac events. The trial continues to follow up patients to the co-primary endpoint of OS and for planned long-term follow-up analysis. Limitations of the study include a lack of blinding to treatment regimen and that the triplet control regimen did not include a proteasome inhibitor for all patients, which would be considered a current standard of care in many parts of the world. Conclusions The KRdc combination was well tolerated and was associated with both an increased percentage of patients achieving at least a very good partial response and a significant PFS benefit compared to immunomodulatory-agent-based triplet therapy. Trial registration ClinicalTrials.gov ISRCTN49407852.

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Oral lenalidomide plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7518 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7518-7518 ◽

Cited By ~ 6

Author(s):

A. Palumbo ◽

P. Falco ◽

G. Benevolo ◽

L. Canepa ◽

S. D’Ardia ◽

...

Keyword(s):

Multiple Myeloma ◽

Multicenter Trial ◽

Hematologic Toxicity ◽

Newly Diagnosed ◽

Cutaneous Toxicity ◽

Cutaneous Eruption ◽

Level 3 ◽

Immunomodulatory Drug ◽

Grade 3 ◽

Dose Levels

7518 Background: Lenalidomide (Revlimid) is a novel oral immunomodulatory drug active in refractory multiple myeloma (MM). In this multicenter trial, we evaluate the effect of the combination lenalidomide, melphalan and prednisone (R-MP). Methods: Patients (pts) with newly diagnosed symptomatic MM ≥ 65 years received 9 courses of lenalidomide (21 days every 4–6 weeks) plus MP (4 days every 4–6 weeks). The trial was designed to asses toxicity and efficacy of R-MP combination. Four dose levels were tested (table 1). Each cohort included 6 pts, with additional 15 pts in level 3 and 4. Dose limiting toxicity (DLT) was defined as: grade ≥ 3 non-hematologic toxicity; grade 4 hematologic toxicity (with neutropenia lasting >7 days); treatment delay due to toxicity during the first cycle. All pts received ciprofloxacin and aspirin as prophylaxis. Results: At present, 50 pts (median age 71) received at least one R-MP course. No DLTs were observed in levels 1 and 2. In level 3, 1 pt experienced DLT (grade 4 neutropenia > 7 days). In level 4, 3 pts showed DLTs (neutropenic fever, grade 3 cutaneous toxicity, pulmonary embolism and cycle 2 delay due to neutropenia). After 1 cycle, no one was in complete remission (CR) (according to the EBMT/IBMTR criteria), 51% of pts showed a response of 50–99% (PR) and 49% a response <50%, no progressive disease (PD) occurred. After 3 cycles, CR was observed in 10% of pts, PR in 60% and response <50% in 30%, no PD occured. Major grade 3–4 adverse events were hematological toxicities: neutropenia (58%) and thrombocytopenia (21%). Major grade 3–4 non-hematological toxicities were cutaneous eruption (11%), infections (5%) and febrile neutropenia (3%). Neuropathy was not observed and only one thromboembolism was recorded. Conclusions: R-MP was well tolerated with a manageable toxicity. Significant response rate was observed. It represents a feasible and promising approach for elderly newly diagnosed pts. An update of these data will be presented. [Table: see text] [Table: see text]

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