Outcomes of anti-CD38 isatuximab plus pomalidomide and dexamethasone in five relapsed myeloma patients with prior exposure to anti-C38 daratumumab: case series

© 2022 The Authors. Published by Taylor & Francis and International Society of Hematology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1080/16078454.2022.2028978Objectives: Daratumumab is the first anti-CD38 monoclonal antibody (Mab) used to treat myeloma in the newly diagnosed setting and in the relapsed setting. Isatuximab, another Mab targeting a specific epitope on the CD38 receptor, was recently approved in the UK in combination with pomalidomide and dexamethasone (IsaPomDex) to treat myeloma patients who received three prior lines of therapy. However, there is a lack of understanding of whether using a prior anti-CD38 Mab (e.g. daratumumab) can affect the efficacy of another Mab (e.g. isatuximab), when the latter is used to treat a subsequent relapse.Methods: We performed a UK-wide outcomes study of IsaPomDex in the real-world. In this case series, we report a detailed descriptive analysis of the characteristics and clinical outcomes of five IsaPomDex patients in UK routine practice (Patients I to V), with a prior exposure to daratumumab.Results: Age range was 51-77 years with two patients >70 and three patients <70 years. The cytogenetic risk was standard in two patients, high in two patients and not known in one patient. Prior daratumumab regimen were monotherapy (dara-mono) in one patient (II), and daratumumab with bortezomib and dexamethasone (DVd) in four patients. Responses to prior daratumumab were: very good partial response (VGPR) in two patients (I and III), minor response-stable disease (MR-SD) in one patient (II), and progressive disease (PD) in two patients (IV and V). Median (range) number of IsaPomDex cycles received was 2 (1-4). Outcomes of IsaPomDex were PD in three patients (II, IV and V) and a response in two patients. Response categories were: MR-SD in patient I and PR in patient III.Discussion: Despite the limitations of our case series, we described the first UK real-world report of IsaPomDex outcomes in myeloma patients with a prior exposure to daratumumab.Conclusion: Large prospective studies are required to further evaluate myeloma outcomes in this setting.Published versio

Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study

© 2022 The Authors. Published by Taylor & Francis. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1080/16078454.2022.2082725Objectives There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. Methods The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2–5) and high grade (≥G3) infections. Results In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2–8), 23.4% of patients experienced ≥1 any grade (G2–5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16–75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (<PR) (p = 0.048) are independent predictors of ≥ G3 infections. Conclusion Our study described initial results of infection burden during IsaPomDex treatment. We recommend close monitoring particularly in elderly patients with co-morbidities, the effective use of an-infective prophylaxis, as well as optimal vaccination strategies, to limit infections

Efficacy of isatuximab with pomalidomide and dexamethasone in relapsed myeloma: Results of a UK-wide real-world dataset

This is an accepted manuscript of a paper due to be published by Lippincott, Williams & Wilkins in HemaSphere (in press). The accepted manuscript of the publication may differ from the final published versionReal-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma (RRMM) patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centres. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥PR), and adverse events (AEs). In a total cohort 107 patients, median follow up (IQR) was 12.1 months (10.1-18.6 months), median age (IQR) was 69 years (61-77). Median (IQR) Charlson Co-morbidity index (CCI) score was 3 (2- 4); 43% had e-GFR<60 ml/min. Median (IQR) number of prior therapies was 3 (3-3). Median (IQR) number of IsaPomDex cycles administered was 7 (3-13). ORR was 66.4%, with responses categorised as ≥VGPR: 31.8%, PR: 34.6%, SD: 15.9%, PD: 15% and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months There was no statistical difference in median PFS by age (<65: 10.2 vs. 65-74 13.2 vs. ≥75: 8.5 months, log-rank p=0.4157), by CCI score (<4: 10.2 months vs. ≥4: 13.2, log-rank p=0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 vs. <60: 7.9 months, log-rank p=0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%) and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real-world, comparable to ICARIA-MM trial

Frailty subgroup analysis of isatuximab with pomalidomide and dexamethasone in a UK-wide real-world cohort of relapsed myeloma patients

This is an accepted manuscript of an article published by Wiley on 31/01/2023, available online: https://doi.org/10.1111/bjh.18672 The accepted version of the publication may differ from the final published version.Published versio