Alternate-day dosing of pomalidomide in relapsed/ refractory multiple myeloma: a multicenter, single-arm phase 2 trial.
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SUBMITTER: Zander T
PROVIDER: S-EPMC9991905 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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Alternate-day dosing of pomalidomide in relapsed/ refractory multiple myeloma: a multicenter, single-arm phase 2 trial.
Zander Thilo T Pabst Thomas T Schär Sämi S Aebi Stefan S Mey Ulrich U Novak Urban U Lerch Erika E Rhyner Agocs Gaëlle G Goede Jeroen J Maniecka Zuzanna Z Hayoz Stefanie S Rüfer Axel A Renner Christoph C Driessen Christoph C
Leukemia 20230112 3
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Project description:BackgroundPomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients.MethodsAdult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR).ResultsSeventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported.ConclusionsPomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients.Trial registrationThe study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).
| S-EPMC9250185 | biostudies-literature
Project description:Treatment options for patients with heavily pretreated relapsed and/or refractory multiple myeloma remain limited. We evaluated a novel therapeutic regimen consisting of carfilzomib, pomalidomide, and dexamethasone (CPD) in an open-label, multicenter, phase 1, dose-escalation study. Patients who relapsed after prior therapy or were refractory to the most recently received therapy were eligible. All patients were refractory to prior lenalidomide. Patients received carfilzomib IV on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m(2)), pomalidomide once daily on days 1 to 21 (4 mg as the initial dose level), and dexamethasone (40 mg oral or IV) on days 1, 8, 15, and 22 of 28-day cycles. The primary objective was to evaluate the safety and determine the maximum tolerated dose (MTD) of the regimen. A total of 32 patients were enrolled. The MTD of the regimen was dose level 1 (carfilzomib 20/27 mg/m(2), pomalidomide 4 mg, dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in ≥60% of all patients, including 11 patients with grade ≥3 anemia. Dyspnea was limited to grade 1/2 in 10 patients. Peripheral neuropathy was uncommon and limited to grade 1/2. Eight patients had dose reductions during therapy, and 7 patients discontinued treatment due to AEs. Two deaths were noted on study due to pneumonia and pulmonary embolism (n = 1 each). The combination of CPD is well-tolerated and highly active in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT01464034.
| S-EPMC4643003 | biostudies-literature
Project description:This phase 1b dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly for 4 weeks, followed by every 2 weeks), pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg (weekly) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n = 8], 10 [n = 31], or 20 [n = 6] mg/kg). Patients received a median of 3 (range, 1-10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 patients (42%) remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 treatment-emergent adverse event was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pretreated patients with RRMM. The 10 mg/kg weekly/every 2 weeks isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov as #NCT02283775.
| S-EPMC6659612 | biostudies-literature
Project description:The addition of clarithromycin enhances the efficacy of lenalidomide plus dexamethasone in treatment-naive multiple myeloma (MM). We conducted a phase 2 trial to evaluate the safety and efficacy of clarithromycin, pomalidomide, and dexamethasone (ClaPd) in relapsed or refractory multiple myeloma (RRMM) with prior lenalidomide exposure. One hundred twenty patients with a median of 5 prior lines of therapy received clarithromycin 500 mg orally twice daily, pomalidomide 4 mg orally on days 1 to 21, and dexamethasone 40 mg orally on days 1, 8, 15, and 22 of a 28-day cycle. The overall response rate (ORR) was 60% with 23% achieving at least a very good partial response. There was no statistical difference in response rates for patients who were refractory to lenalidomide (ORR, 58%), bortezomib (ORR, 55%), or both lenalidomide and bortezomib (ORR, 54%). Median progression-free survival (PFS) for the cohort was 7.7 months and median overall survival (OS) was 19.2 months. A history of dual-refractoriness to lenalidomide and bortezomib did not significantly impact either PFS or OS. The most common toxicities were neutropenia (83%), lymphopenia (74%), and thrombocytopenia (71%). The most common grade ≥3 toxicities included neutropenia (58%), thrombocytopenia (31%), and anemia (28%). ClaPd is an effective combination in RRMM with response and survival outcomes that are independent of lenalidomide- or bortezomib-refractory status. Toxicities are manageable with low rates of nonhematologic or high-grade events. ClaPd is a convenient, all-oral option in RRMM with comparable efficacy to other highly active, 3-drug, pomalidomide-based combinations. This trial was registered at www.clinicaltrials.gov as #NCT01159574.
| S-EPMC6391672 | biostudies-literature
Project description:This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.
| S-EPMC10866745 | biostudies-literature
Project description:BackgroundThe immunomodulatory agent pomalidomide in combination with low-dose dexamethasone has demonstrated efficacy and safety for the treatment of relapsed and refractory multiple myeloma (RRMM) in phase 2 and 3 trials. However, these trials enrolled very few Asian patients.MethodsThis phase 2 study investigated pomalidomide plus low-dose dexamethasone in 36 Japanese patients with RRMM after ≥2 prior therapies.ResultsPatients enrolled in the study had a relatively high disease burden (81 % Durie-Salmon stage II or III) and were heavily pretreated (median, 6.5 prior antimyeloma regimens). The overall response rate was 42 % (1 patient with complete response and 14 with partial response), with an additional 44 % (16 patients) achieving stable disease (SD). Response rates in patients aged ≤65 years and >65 years were 47 and 35 %, respectively. None of the five patients with extramedullary disease achieved a response, with three of them maintaining SD of short duration. Median progression-free survival was 10.1 months after a 7.7-month median follow-up, and the median overall survival was not reached. The most frequent grade ≥3 adverse events (AEs) were neutropenia (64 %), anemia (42 %), and thrombocytopenia (31 %). The most frequent nonhematologic grade ≥3 AEs were pneumonia and decreased appetite (8 % each). Adverse events in patients aged >65 years were similar to those in patients aged ≤65 years, except for a higher rate of grade ≥3 pneumonia.ConclusionsCollectively, the results of this study demonstrate that pomalidomide plus low-dose dexamethasone is an effective and safe treatment for Japanese patients with RRMM, although careful attention needs to be paid to serious infections.Trial registrationClinicaltrials.gov NCT02011113.
| S-EPMC4835896 | biostudies-literature
Project description: Not available
| S-EPMC6068091 | biostudies-literature
Project description:In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose-limiting. Per 3 + 3 phase I design, an additional three patients were enrolled to DL1, with no further dose-limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll three additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ≥ partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ≥ stable disease. The most common adverse events (≥grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.
| S-EPMC6005710 | biostudies-literature
Project description:Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Per protocol, all patients (N = 112) had received lenalidomide in their most recent prior regimen (75.0% lenalidomide refractory). ORR was 77.7% (76.2% in lenalidomide-refractory patients); median follow-up was 17.2 months. Median PFS was not reached (1-year PFS rate 75.1%). The most common hematologic grade 3/4 treatment-emergent adverse event was neutropenia (62.5%). Grade 3/4 infections were reported in 31.3% of patients, including 13.4% with grade 3/4 pneumonia. These results demonstrate the safety and efficacy of pomalidomide-based therapy as early as second line in patients with RRMM, even immediately after lenalidomide failure, indicating that switching from the immunomodulatory agent class is not necessary.
| S-EPMC7685974 | biostudies-literature
Project description:Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N = 103) received a median (range) of 4 (1-13) prior therapies; 76% received ≥3 prior therapies. The safety profile of daratumumab plus pom-dex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade ≥3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Among patients with a complete response or better, 29% were MRD negative at a threshold of 10-5 Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as #NCT01998971.
| S-EPMC5570682 | biostudies-literature