Pomalidomide- and dexamethasone-based regimens in the treatment of refractory/relapsed multiple myeloma

Fotiou, Despina; Gavriatopoulou, Maria; Terpos, Evangelos; Dimopoulos, Meletios Α.

doi:10.1177/20406207221090089

Cited by 12 publications

(5 citation statements)

References 83 publications

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“…Помалидомид -иммуномодулирующий препарат 3го поколения, зарегистрированный для лечения па циентов с р / р ММ, которые получили по крайней ме ре 2 курса терапии, включавших леналидомид и бор тезомиб (двойная рефрактерность) и у которых отмечалось прогрессирование заболевания непосред ственно на фоне последней линии терапии или в пре делах 60 дней после ее окончания. В настоящее время сочетание помалидомида и дексаметазона (Pd) стало основой для тройных схем (триплетов) для лечения р / р ММ, включая комбинации с моноклональными антителами элотузумабом (EloPd), изатуксимабом (IsaPd), даратумумабом (DPd) [9].…”

Section: Discussionunclassified

Case report: pomalidomide as maintenance after salvage autologous stem cell transplantation in a patient with relapsed multiple myeloma

Semochkin,

Lunin,

Vernyuk

et al. 2023

Onkogematologiâ

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Currently, lenalidomide is the only immunomodulatory drug (IMiD) approved for maintenance therapy in patients with newly diagnosed multiple myeloma who have received high-dose chemotherapy and autologous stem cell transplantation (ASCT). The maintenance with lenalidomide showed an advantage over placebo or observation for both progression-free and overall survival in a series of phase 3 randomized trials. Salvage ASCT can be performed after disease relapse in case of a long-term response after the first transplantation or if this option has not been performed before. Pomalidomide is a third-generation IMiD approved for the treatment of relapsed and refractory multiple myeloma, which is efficient in patients with resistance to lenalidomide and proteasome inhibitors. Structurally, lenalidomide and pomalidomide are similar, and therefore the latter can also be considered as a drug for maintenance, however, there are no relevant phase 3 randomized trials. In this article, we present a clinical case of a 60-year-old patient with newly diagnosed multiple myeloma who progressed after 2 lines of induction therapy, which included lenalidomide and two proteasome inhibitors (bortezomib, ixazomib). The use of Pd combination (pomalidomide, dexamethasone) made it possible to achieve a repeated response and implement of salvage ASCT. The second ASCT was carried out only 12 months later after the first due to the COVID-19 pandemic. Subsequent long-term maintenance therapy with pomalidomide resulted in a complete response and minimal residual disease negativity. The resulting response has persisted at the time of this writing for over 2 years. To discuss the presented clinical case, the data of the French phase 2 IFM 2013-01 study were used, in which patients with failed first-line transplantation in case of relapse received PCd (pomalidomide, cyclophosphamide, dexamethasone) induction, salvage ASCT, and maintenance by Pd until disease progression. Pomalidomide may be an acceptable substitute for lenalidomide in patients with prior intolerance or refractory to this IMiD.

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Section: Discussionunclassified

Case report: pomalidomide as maintenance after salvage autologous stem cell transplantation in a patient with relapsed multiple myeloma

Semochkin,

Lunin,

Vernyuk

et al. 2023

Onkogematologiâ

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“…Pomalidomide is a second-generation IMiD that was initially approved in combination with low-dose dexamethasone by the Food and Drug Administration (FDA) in 2013 [ 3 ]. Pomalidomide exhibits several antitumor activities in terms of immunomodulatory response, marrow stroma interaction, activation of proteasomal degradation pathways, and anti-angiogenic activity [ 4 ]. These characteristics have made pomalidomide an effective foundation for combined use with other classes of drugs in MM treatment.…”

Section: Introductionmentioning

confidence: 99%

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone

Alkharabsheh¹,

Bellman²,

Mahmoudjafari³

et al. 2023

J Hematol

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Background Daratumumab, pomalidomide, and dexamethasone (DPd) is an effective option for treatment of patients with relapsed/refractory multiple myeloma (RRMM). In this study, we sought to analyze the risk of hematological and non-hematological toxicities in patients who responded to DPd treatment. Methods We analyzed 97 patients with RRMM who were treated with DPd between January 2015 and June 2022. The patients and disease characteristics, as well as safety and efficacy outcomes were summarized as descriptive analysis. Results The overall response rate for the entire group was 74% (n = 72). The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common grade III/IV non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%). The incidence of dose reduction/interruption was 76% (55/72), which was due to hematological toxicity in 73% of the cases. The most common reason for discontinuing treatment was disease progression in 61% (44 out of 72 patients). Conclusions Our study revealed that patients who respond to DPd are at high risk of dose reduction or treatment interruption because of hematological toxicity, typically due to neutropenia and leukopenia leading to increased risk of hospitalization and pneumonia.

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“…In the MM‐002 study, which was the basis of this approval, patients who received pomalidomide with low‐dose dexamethasone achieved an overall response rate of 33%, median progression‐free survival of 4.2 months, and median overall survival (OS) of 16.5 months [2]. Pomalidomide‐dexamethasone (Pd) has since been tested in triplet combinations with other antimyeloma agents and is currently approved for relapsed and refractory multiple myeloma in combination with bortezomib, daratumumab, isatuximab, or elotuzumab [3–7]. The outcomes of patients treated with Pd have been reported in several real‐world studies performed in smaller populations [8–15].…”

Section: Introductionmentioning

confidence: 99%

“…or elotuzumab [3][4][5][6][7]. The outcomes of patients treated with Pd have been reported in several real-world studies performed in smaller populations [8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The real‐world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies

Szabo,

Thorsen,

Iversen

et al. 2023

eJHaem

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Pomalidomide‐dexamethasone (Pd) has been a standard care treatment for relapsed and refractory multiple myeloma since 2013. However, the outcomes of Pd after exposure to CD38 antibodies are not known. Here we describe the real‐world use and efficacy of pomalidomide in a Danish, nationwide cohort of daratumumab‐exposed patients. We identified 328 patients that were treated with pomalidomide. Of these, 137 received Pd, 65 daratumumab‐pomalidomide‐dexamethasone (DPd), 43 pomalidomide‐cyclophosphamide‐dexamethasone (PCd), 19 carfilzomib‐pomalidomide‐dexamethasone (KPD), 11 pomalidomide‐bortezomib‐dexamethasone (PVd), and 52 pomalidomide in other combinations. Patients treated with Pd in this cohort had a partial response or better (≥ PR) rate of 35.8% and median time to next treatment (mTNT) of 4.9 months, almost identical to the results of previous prospective clinical trials. Although treatment with the various pomalidomide‐containing triplet regimens resulted in higher ≥ PR rates (PCd: 46.5%, PVd: 63.6%, DPd: 55.4%, KPd: 63.2%), the mTNT achieved was not significantly better than with Pd in most cases (PCD: 5.4, PVD: 5.3, DPD: 4.7 months). The exception to this was KPd (mTNT 7.4 months), but this regimen was mainly used earlier in the course of the disease (median time from diagnosis 2.3 years vs. 3.7–4.3 years). The most important predictor of outcomes was not the choice of index regimen (p = 0.72), but prior exposure (p = 0.0116). Compared to CD38 antibody‐naïve patients, triple‐class‐exposed patients achieved reduced ≥ PR rate (38.0% vs. 47.3%), shorter mTNT (4.0 vs. 5.9 months), and shorter median overall survival (12.4 vs. 24.2 months) with pomalidomide treatment.

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Pomalidomide- and dexamethasone-based regimens in the treatment of refractory/relapsed multiple myeloma

Cited by 12 publications

References 83 publications

Case report: pomalidomide as maintenance after salvage autologous stem cell transplantation in a patient with relapsed multiple myeloma

Case report: pomalidomide as maintenance after salvage autologous stem cell transplantation in a patient with relapsed multiple myeloma

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone

The real‐world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies

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