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A panel of internationally recognised KOLs speaks with ecancer about the challenges associated with managing elderly, frail, and renally impaired patients.
The KOLs review and discuss the results of the 2 isatuximab pivotal trials in these difficult-to-treat patients.
A BRIEF OVERVIEW OF THE ISATUXIMAB PIVOTAL STUDIES—ICARIA-MM AND IKEMA
Dr Schjesvold summarises the ICARIA-MM and IKEMA results, highlighting that both studies met the primary endpoint of PFS.
The IKEMA trial compared isatuximab in combination with Kd vs Kd alone. The mPFS was not yet reached at an interim analysis of 21 months, with a 47% reduction in risk of disease progression vs Kd alone (HR=0.531; 95% CI: 0.318, 0.889; P=0.0013).
A more recent analysis of IKEMA with 44 months of follow-up showed a mPFS of 35.7 months for isatuximab + Kd vs 19.2 months with Kd alone (HR=0.58; 95.4% CI: 0.42, 0.79), representing an unprecedented result in a trial that includes lenalidomide-refractory patients.
The ICARIA-MM trial compared isatuximab in combination with Pd vs Pd alone. The ICARIA-MM trial demonstrated a 5-month improvement in mPFS with the addition of isatuximab to Pd (HR=0.596; 95% CI: 0.44, 0.81; P=0.001).
In IKEMA, the most frequent adverse reactions (≥20%) were infusion reactions (46%), hypertension (37%), diarrhoea (36%), upper respiratory tract infection (36%), fatigue (28%), dyspnoea (28%), insomnia (24%), pneumonia (29%), bronchitis (23%), and back pain (22%).
In ICARIA-MM, the most frequent adverse reactions (≥20%) were neutropenia (47%), infusion reactions (38%), pneumonia (31%), upper respiratory tract infection (28%), diarrhoea (26%), and bronchitis (24%).
THE IMPORTANCE OF ANTIMYELOMA THERAPY IN PATIENTS WITH RENAL IMPAIRMENT
Professor Dimopoulos explains that ‘reversal of renal impairment is of paramount importance for both the quality of life of the patients and, in some cases, for their overall survival’. He also shares that ‘one of the factors associated with a high probability for reversal of renal impairment is response to the antimyeloma therapy’.
The panel goes on to review the isatuximab efficacy and safety data in patients with renal impairment.
In IKEMA, a very low PFS hazard ratio of 0.27 (95% CI: 0.11, 0.66) was seen and equated to a 73% reduction in the risk of disease progression or death (n=43 with SARCLISA + Kd; n=18 with Kd alone). In ICARIA-MM, mPFS was more than doubled in the isatuximab arm (n=55 with SARCLISA + Pd; n=49 with Pd alone).
In terms of renal response, more patients achieved CrR when isatuximab was added to Pd or Kd vs Pd or Kd alone. In IKEMA, CrR was 52% with isatuximab + Kd vs 31% with Kd alone. In ICARIA-MM, CrR was 71.9% with isatuximab + Pd vs 38.1% with Pd alone.
In IKEMA, ≥ Grade 3 AEs were similar in the isatuximab + Kd and Kd arms, serious AEs were lower in the isatuximab arm, and the rate of serious AEs and discontinuation rates due to AEs were lower in the isatuximab arm.
In ICARIA-MM, ≥ Grade 3 AEs and serious AEs were higher in the isatuximab + Pd arm, but this did not translate into increased incidence of Grade 5 AEs. As with IKEMA, discontinuation rates due to AEs were lower in the isatuximab arm.
CHALLENGES ASSOCIATED WITH TREATING PATIENTS WHO ARE ELDERLY AND/OR FRAIL
The panel then goes on to discuss the clinical management of elderly and frail patients (n=32 with SARCLISA + Pd; n=29 with Pd alone), highlighting the need to avoid toxicity-related mortality and maintain quality of life.
Dr Schjesvold reviews results from the ICARIA-MM study.
Elderly patients, defined as ≥75 years of age, constituted about 20% of the patients in the trial. In this subgroup, the mPFS of 11.4 months closely mirrored the results in the overall population and more than doubled mPFS vs the Pd arm (4.47 months), with a hazard ratio of 0.479 (95% CI: 0.242-0.946).
A post hoc analysis of ICARIA-MM assessed patients who were frail based on age, comorbidities, and Eastern Cooperative Oncology Group performance status. The addition of isatuximab to Pd (n=48) doubled mPFS vs Pd alone (n=38) (9.0 months vs 4.5 months). These results were consistent with the overall population, although not statistically significant.
In terms of safety, the incidences of ≥ Grade 3 AEs and serious AEs were higher in the isatuximab + Pd arm for both patients ≥75 years and for patients who are frail.
CLOSING STATEMENTS
The discussion concludes on the topic of the best therapy for patients who progressed while on lenalidomide. For first relapse, Dr Schjesvold states a clear preference for an anti-CD38 antibody plus Kd, highlighting that the updated results from IKEMA are the best ever seen in this population.
ecancer's filming has been kindly supported by Sanofi through the ecancer Global Foundation.
The content of this video is based on the SARCLISA® (isatuximab) EU Summary of Product Characteristics which can be accessed by clicking the link below:
https://www.ema.europa.eu/en/documents/product-information/sarclisa-epar-product-information_en.pdf
Sanofi does not recommend the use of its products in any manner inconsistent with that described in the label available in your country. Please refer to your local product labelling information before prescribing; view your country-specific product labelling information here. If this link does not directly go to your country-specific product labelling information, it can be accessed here.
MAT-GLB-2203116(1.0) 08/22
