Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials

Mushtaq, Adeela; Ahmad, Iftikhar; Hassan, Hamza; Lakhani, Midhat; Sagar, Fnu; Kamal, Ahmad; Zahid, Umar; Ali, Zeeshan; Razzaq, Faryal; Zar, Muhammad Abu; Hassan, Syeda Fatima; Safdar, Ahmad; Raychaudhuri, Sreejata; Anwer, Faiz

doi:10.1016/j.clml.2019.04.003

Cited by 13 publications

(9 citation statements)

References 33 publications

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“…In the context of the effectiveness outcomes of POWERFUL, the observed ORR is similar to the rates reported for the POM/LoDex arm in the phase 3 MM-003 trial (31%), as well as the 32.6% ORR reported in the subsequent STRATUS MM-010 trial, which included heavily pretreated patients with RRMM [16,17]. The ORR in POWERFUL is also similar to the 32.1% rate reported in the phase 2 MM-014 trial for the cohort of patients receiving POM/LoDex immediately after LEN-based treatment failure and the 35.7% rate reported in a recent meta-analysis of pooled data derived from 16 phase 2 and 3 clinical trials [7,21]. The median DoR in POWERFUL (15.8 months) was within the range of that reported in the clinical trial setting (8.3-16.6 months) [7,15], while the TTR was somewhat longer (3.2 vs. 1.9 months) [15].…”

Section: Discussionsupporting

confidence: 70%

Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study

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Repousis

Lalayanni

et al. 2021

JCM

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The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.

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Section: Discussionsupporting

confidence: 70%

Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study

Terpos

Repousis

Lalayanni

et al. 2021

JCM

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“…Other combinations, such as the addition of pomalidomide to Kd (KPd), have been evaluated in 3 phase 1/2 RCTs (192 heavily treated patients who had a mean of 3.3 prior lines of therapy), reporting an ORR of 77.1% and a median PFS of 15.3 months [ 60 – 63 ]. Only one study reached an OS of 12 months [ 64 ]. So far, no phase 3 RCTs for this combination have been planned.…”

Section: The Arsenal Of New Drugs and Therapies With No Cross Resistance With The Therapeutic Standards Used In First Line To Datementioning

confidence: 99%

“…Pomalidomide has shown favorable results in combination with other agents in clinical studies in which refractoriness and/or at least previous treatment with lenalidomide were the inclusion criteria. With dexamethasone (Pd), an improvement in OS was reported compared to dexamethasone alone [ 52 ], and the combination of pomalidomide with cyclophosphamide (PCd) has recently demonstrated better efficacy in phase 2 RCTs (median PFS 9.5 months) [ 64 ]. In combination with isatuximab, Pd showed clinical benefits compared to Pd alone in a phase 3 trial, with a higher incidence of some grade 3-4 AEs, but fewer AE-associated discontinuations [ 10 , 67 ].…”

Section: The Arsenal Of New Drugs and Therapies With No Cross Resistance With The Therapeutic Standards Used In First Line To Datementioning

confidence: 99%

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

et al. 2022

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The increase in the number of therapeutic alternatives for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM) patients has widened the clinical scenario, leading to a level of complexity that no algorithm has been able to cover up to date. At present, this complexity increases due to the wide variety of clinical situations found in MM patients before they reach the status of relapsed/refractory disease. These different backgrounds may include primary refractoriness, early relapse after completion of first-line therapy with latest-generation agents, or very late relapse after chemotherapy or autologous transplantation. It is also important to bear in mind that many patient profiles are not fully represented in the main randomized clinical trials (RCT), and this further complicates treatment decision-making. In RRMM patients, the choice of previously unused drugs and the number and duration of previous therapeutic regimens until progression has a greater impact on treatment efficacy than the adverse biological characteristics of MM itself. In addition to proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and corticosteroids, a new generation of drugs such as XPO inhibitors, BCL-2 inhibitors, new alkylators and, above all, immunotherapy based on conjugated anti-BCMA antibodies and CAR-T cells, have been developed to fight RRMM. This comprehensive review addresses the fundamentals and controversies regarding RRMM, and discusses the main aspects of management and treatment. The basis for the clinical management of RRMM (complexity of clinical scenarios, key factors to consider before choosing an appropriate treatment, or when to treat), the arsenal of new drugs with no cross resistance with previously administered standard first line regimens (main phase 3 clinical trials), the future outlook including the usefulness of abandoned resources, together with the controversies surrounding the clinical management of RRMM patients will be reviewed in detail.

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“…[6] Most of these mechanisms are common with the other IMiDs derived from thalidomide. [7,8] The major pulmonary adverse event reported with pomalidomide is infectious pneumonia [9][10][11] (occurs in 15 to 20% of treated patients), related to neutropenia. Thromboembolic events, which are also reported with Lenalidomide and Thalidomide, occur in 1% of patients treated with pomalidomide.…”

Section: Discussionmentioning

confidence: 99%

Pomalidomide-induced lung injury: A case report

et al. 2023

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Rationale: Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma. Patient concerns: A 72-years-old male, treated for multiple myeloma with dexamethasone, pomalidomide and daratumumab, presented dyspnea, hypoxemia, biological inflammatory syndrome, ground glass opacities on computed tomography scan (CT-scan) and lymphocytic and eosinophilic alveolitis, with no specific cytologic or microbiological findings, 2 months after pomalidomide initiation. Intervention and outcome: Antibiotics were started after bronchoscopy. No improvement was noted in dyspnea and biological inflammatory syndrome after 5 days of treatment. Pomalidomide was then discontinued, with continuation of Daratumumab-Dexamethasone, resulting in a rapid recovery of symptoms and CT-scan anomalies. No recurrence of dyspnea was observed during the 15 months of follow-up. Diagnoses: Pomalidomide-induced lung injury Lessons: Pomalidomide-induced lung injury is a rare and serious adverse event that can occur early after Pomalidomide introduction. As pomalidomide use is increasing, the identification of drug toxicity as a possible cause of lung injury appears important. We report a rapid recovery of symptoms and CT-scan anomalies after pomalidomide discontinuation.

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Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials

Cited by 13 publications

References 33 publications

Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study

Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

Pomalidomide-induced lung injury: A case report

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