Page 223 - Haematologica Vol. 109 - July 2024

ARTICLE - Carfilzomib, thalidomide and dexamethasone (KTd) in RRMM S. Ninkovic et al.
ulation compared to the overall population of the ENDEAVOR and A.R.R.O.W. trials. In our cohort of patients, while dyspnea was the most commonly reported adverse event of any grade and the most common ≥3 grade event, documented cardiac failure was reported in a single, non-Asian patient. One ex- planation for the reduced rates of cardiac failure seen in our study may be the benefit of developed clinical experience with carfilzomib at the time of study initiation and routine measures to mitigate risks associated with carfilzomib ther- apy including strict monitoring and management of systemic hypertension, fluid balance and symptom-driven carfilzomib dose delays and reductions. Indeed, carfilzomib dose reduc- tion rates in the ENDEAVOR, A.R.R.O.W. and ASPIRE studies were comparable to those in our study, and while these did not routinely report on carfilzomib dose delay, 42% of our cohort of patients experienced an adverse event-triggered carfilzomib dose delay.10,14,30 Another adverse event of special interest, carfilzomib-induced thrombotic thrombocytopenic purpura, while rare has been reported in association with carfilzomib previously.31 Both of our patients who developed this adverse event were Asian and developed a non-immune thrombocytopenia with a nadir platelet count of <30x109/L, blood film features of microangiopathic hemolysis with red cell fragmentation, and ADAMTS-13 levels >10%, thus excluding a diagnosis of de novo thrombotic thrombocytopenic purpura. Both were on the 56 mg/m2 dose, developed features early in treatment (first and third cycle) and responded to immu- nosuppression and plasma exchange.
In conclusion, KTd demonstrates favorable tolerability with commonly encountered toxicities that require proactive man- agement in routine clinical practice. KTd is efficacious in pa- tients with RRMM irrespective of Asian or non-Asian ethnicity, and irrespective of prior exposure to immunomodulatory drugs or proteasome inhibitors in first-line treatment of multiple myeloma. This combination may be an alternative to KRd in circumstances in which delivery of lenalidomide is limited by cost, access, or renal impairment. The use of carfilzomib until disease progression may be considered to further improve the
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PFS as this has been shown to be safe in the ENDEAVOR study.14
Disclosures
SJH reports consulting or advisory roles for Celgene, Hoff- man-La Roche AG, Genetech USA, HaemaLogiX, Janssen Global Services, and Novartis and research support from HaemaLogiX and Janssen Global Services. HQ reports con- sulting or advisory roles for Amgen, Antengene, Bristol-Myers Squibb/Celgene, Celgene, GSK, Janssen-Cilag, Karyopharm Therapeutics, Pfizer, Roche, and Sanofi and research support from Amgen, Bristol-Myers Squibb/Celgene, Celgene, GSK, Karyopharm Therapeutics and Sanofi. All other authors have no conflicts of interest to disclose.
Contributions
WJC, HQ, PM, and BD developed the concept and design of the study. SN, SJH, JJL, NM, JHJ, JE, VMC, NH, KK, RE, BA, SMB, SYH, RR, WJC, and HQ managed patients and partic- ipated in the collection of clinical data. DE managed the data collection and assembly. BB performed the statistical analyses. SN and HQ interpreted the data and wrote the manuscript. All authors critically revised the manuscript and reviewed and approved the final version.
Acknowledgments
The authors thank all the patients, families, caregivers, research nurses, study coordinators, sub-investigators and support staff who contributed to this study.
Funding
This study was supported by a grant from Amgen which also provided the carfilzomib used in this study, and by funding from the CASS (Contributing to Australian Scholarship and Science) foundation.
Data-sharing statement
Original data and protocols may be obtained upon written request.
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