Bortezomib-Pomalidomide-Dexamethasone (VPD) As Novel Induction Therapy in Newly-Diagnosed Multiple Myeloma: Early Safety Data from an Ongoing Single Arm Phase-II Investigator-Initiated Clinical Trial (PRIME Study)
Blood
; 138:2752, 2021.
Article
in English
| EMBASE | ID: covidwho-1582239
ABSTRACT
Introduction:
Pomalidomide is a third-generation immunomodulatory drug approved for relapsed and/or refractory Multiple Myeloma (RRMM). In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone demonstrated superior efficacy in patients with RRMM. PRIME study (CTRI/2019/10/021618) is testing this combination in Newly Diagnosed Multiple Myeloma (NDMM)Aim:
To determine safety of Pomalidomide in combination with Bortezomib and dexamethasone (VPD) in NDMM Studydesign:
A prospective, single arm, phase II study from a tertiary center. Both transplant eligible and ineligible patients with NDMM aged between 18-70 years are being recruited in the study. Patients with Plasma cell leukemia, POEMS and amyloidosis were excluded. The regimen consists of weekly Bortezomib 1.3mg/sq.m (subcutaneous), Tab. Pomalidomide 2-4mg once daily for 21days, and Tab Dexamethasone 20mg twice weekly, with the cycle repeating every 28 days, 9-12 cycles. Here we report the adverse events (AE) by NCI CTCAE v5.0, upon recruiting 26 patients, as predetermined in the study.Results:
Of the proposed 45-50 patients, 26 patients were enrolled in the study between April 2020 to May 2021 and 23 (88.4%) have completed 4 cycles of VPD. The median age is 55years (18-70), and gender ratio 11. At disease presentation, bone lesions were the commonest (96.2%, n=25), IMWG high risk cytogenetics were seen in 42.4% (n=11), RISS-2 in 69.3% (n=18), IgG kappa paraproteinemia in 54% (n=14) patients and ECOG performance score 2-3 in 57.6%(n=15). Ten (38.5%) patients have completed 9 cycles, and 3 underwent auto-transplant (between Cycle 4 & 6). Protocol adherence was 96.1% (25/26 patients). Table-1 shows drug-induced toxicity, hematological toxicities were the commonest. Two patients withdrew consent in view of bortezomib-induced peripheral neuropathy. Serious adverse events (SAE) were reported in 9 (34.6%) patients and were considered unrelated to the regimen by the safety committee (PSVT=1, Bony pain=2, dyspnea=1, pneumonia=1, constipation=1, diarrhea=1, hypotension=1) and one death due to SARS-CoV2 pneumonia. Treatment delays of 2 weeks in 4 patients (SARS-CoV2 = 3, Syncope = 1) After 4 cycles (n=23), 6 (26%) patients were in stringent Complete Response (sCR), 17(74%) in Very Good partial response (VGPR) and 13 (56.5%) are Measurable Residual Disease (MRD) negative. Of 10 patients who completed cycle 9, 9 were MRD negative and 1 showed disease progression.Conclusion:
Safety data from the PRIME study demonstrates that VPD regimen has a favorable tolerance profile in patients with NDMM. Early efficacy signals are encouraging, and recruitment continues. [Formula presented] Disclosures Radhakrishnan Dr Reddy's Laboratories Honoraria, Membership on an entity's Board of Directors or advisory committees;Emcure Pharmaceuticals Research Funding;Intas Pharmaceuticals Research Funding;Janssen India Honoraria;NATCO Pharmaceuticals Research Funding;Novartis India Membership on an entity's Board of Directors or advisory committees;Roche India Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;AstraZeneca India Honoraria, Speakers Bureau;Bristol-Myers-Squibb India Membership on an entity's Board of Directors or advisory committees, Research Funding;Cipla Pharmaceuticals India Research Funding;Aurigene Speakers Bureau. Garg Dr Reddys Laboratories Honoraria, Speakers Bureau. Nair Dr Reddy's Laboratories Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Intas pharmaceuticals Honoraria, Speakers Bureau;Mylan pharmaceuticals Honoraria;Novartis India Honoraria;Fresenius Kabi India Honoraria;Cipla Pharmaceuticals Honoraria, Speakers Bureau;Janssen India Honoraria, Speakers Bureau. Chandy Janssen Honoraria;Pfizer Honoraria;Intas Pharmaceuticals Research Funding.
bortezomib; dexamethasone; endogenous, compound; immunoglobulin, kappa, chain; pomalidomide; adult; adverse, drug, reaction; advisory, committee; amyloidosis; blood, toxicity; bone, lesion; cancer, patient; case, report; clinical, article; clinical, trial; conference, abstract; constipation; cytogenetics; diarrhea; drug, combination; drug, safety; drug, therapy; dyspnea; ECOG, Performance, Status; electrocardiograph; faintness; female; funding; gender; human; hypotension; India; male; middle, aged; minimal, residual, disease; multiple, myeloma; nonhuman; pain; peripheral, neuropathy; pharmacokinetics; phase, 2, clinical, trial; phase, 3, clinical, trial; plasma, cell, leukemia; POEMS, syndrome; prospective, study; protocol, compliance; remission; Severe, acute, respiratory, syndrome, coronavirus, 2; side, effect; surgery; therapy, delay; transplantation; young, adult
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Blood
Year:
2021
Document Type:
Article
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