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Letters to the Editor
age group (Table 2). Grade 3-4 anemia was more com- mon in older patients and was observed at comparable rates in both arms, except among patients aged 65-74 years. Patients ≥75 years required more red blood cell transfusions and treatment with erythropoiesis-stimulat- ing agents than younger patients, with older Pd patients requiring these interventions more than Isa-Pd patients (Online Supplementary Table S4). The incidence of grade 4 thrombocytopenia was similar in the two arms across age groups, except for patients ≥75 years (18.8% with Isa-Pd versus 10.7% with Pd) (Online Supplementary Table S5). The need for platelet transfusions was low for all sub- populations and in both treatment arms. Neutropenia and infections were reversible and manageable with sup- portive care (granulocyte colony-stimulating factor/gran- ulocyte-macrophage colony-stimulating factor and antibiotics, respectively).
As shown in Online Supplementary Table S6, the major- ity of TEAE leading to treatment discontinuation were grade ≥3. Infections were the most common TEAE lead- ing to treatment discontinuation in patients ≥75 years in both arms: 9.4% in the Isa-Pd arm and 14.3% in the Pd arm. In the Isa-Pd arm, one patient aged 65-74 (1.5%) and two aged <65 years (3.7%) discontinued treatment due to general disorders. Among patients aged 65-74 and <65 years in the Pd arm, thrombocytopenia was the most frequent TEAE leading to treatment discontinuation (5.7% and 5.9%, respectively).
One limitation of the current ICARIA-MM sub-analy- sis is that the subgroup of patients ≥75 years in ICARIA- MM was about half the size of the other two age groups. Comorbidities and other illnesses that frequently accom- pany elderly patients may have compromised their eligi- bility for the study. However, the same limitation is pres- ent in many MM clinical trials.12 Nonetheless, both study arms had around 20% of patients aged ≥75 years and the oldest patient enrolled in ICARIA-MM was 86 years old, a very advanced age for a third-line trial. Furthermore, the ICARIA-MM study did not assess frailty.13
In contrast to the general observation of a negative prognosis of elderly age in MM, the addition of isatux- imab to pomalidomide and dexamethasone improved progression-free survival, overall response rate, very good partial responses or better rate, and overall survival in elderly patients, consistent with the benefit observed in the overall ICARIA-MM study population. Moreover, isatuximab was well tolerated in older patients (≥75 years), whose treatment lasted longer than that in younger patients, with no increase in fatal TEAE in the Isa-Pd arm versus the Pd arm. A consistent trend toward higher rates of serious TEAE and discontinuation due to TEAE in patients ≥75 years was evident in both arms. Our findings support the use of Isa-Pd in RRMM patients regardless of age.
Okayama Medical Center, Okayama, Japan; 8Hôpital Necker- Enfants Malades, Paris, France; 9Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of South Korea; 10Sanofi CMO, Chilly- Mazarin, France; 11Sanofi Global Oncology, Cambridge, MA, USA; 12Sanofi R&D, Vitry-sur-Seine, France; 13Sanofi R&D, Cambridge, MA, USA and 14Myeloma Unit, Division of Hematology, University of Torino, Azienda-Ospedaliero Universitaria Cittàdella Salute e della Scienza di Torino, Torino, Italy
Correspondence:
SARA BRINGHEN - sarabringhen@yahoo.com
doi:10.3324/haematol.2020.253450
Disclosures: FS: honoraria – Amgen, Celgene, Janssen, MSD, Novartis, Oncopeptides, Sanofi, SkyliteDX and Takeda; membership on an entity’s Board of Directors or advisory committees – Amgen, Celgene, Janssen, MSD, Novartis, Oncopeptides, Sanofi and Takeda. PGR: research funding – Bristol-Myers Squibb, Celgene, Oncopeptides and Takeda; honoraria – Celgene, Janssen, Karyopharm, Oncopeptides, Sanofi and Takeda. TF: membership on an entity’s Board of Directors or advisory committees – Amgen, Celgene, Janssen, Karyopharm, Oncopeptides, Roche and Takeda. AA: honoraria – Amgen, Celgene, Janssen, Sanofi and Takeda; membership on an entity’s Board of Directors or advisory
committees – Amgen, Celgene, Janssen, Sanofi and Takeda.
AS: research funding – Amgen, Celgene, Haemalogix, Janssen Servier and Takeda; honoraria – AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda; consultancy – AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda; speakers’ bureau – Celgene, Janssen and Takeda. AJ: hono- raria – Amgen, Celgene, Janssen-Cilag, Karyopharm and Takeda; membership on an entity’s Board of Directors or advisory
committees – Karyopharm. KS: research funding – AbbVie, Alexion Pharma, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, MSD, Ono Pharmaceutical, Sanofi and Takeda Pharmaceutical;
honoraria – Bristol-Myers Squibb, Celgene, Ono Pharmaceutical
and Takeda Pharmaceutical. LF: honoraria – Amgen, Celgene, Janssen-CILAG and Takeda. SBr: honoraria – Amgen, Bristol-Myers Squibb, Celgene and Janssen; membership on an entity’s Board of Directors or advisory committees – Amgen, Celgene, Janssen and Karyopharm; consultancy – Janssen and Takeda. SG, PLL, SL-G, FC, HvdV and SBe are employed by Sanofi. CKM has no relevant financial relationships to disclose.
Qualified researchers can request access to patient-level data and related study documents including the clinical study report, study proto- col with any amendments, blank case report forms, statistical analysis plan, and dataset specifications. Patient-level data are anonymized, and study documents are redacted to protect the privacy of the trial par- ticipants. Further details on Sanofi’s data-sharing criteria and the process for requesting access are available at: https://www.clinical- studydatarequest.com.
Contributions: FC: the funder’s clinical study director, was responsi- ble for overseeing the ICARIA-MM study. PGR was a co-primary investigator of this study. FS, PGR, TF, AA, AS, AJ, KS, LF, C-KM and SBr were investigators in the study and contributed to data acquisi- tion. PGR, FC and SL-G designed the study. SG and PLL processed the health-related quality of life data and performed the analysis. SL- G, FC, HvdV and SBe contributed to the analysis and interpretation of data for the work. All authors revised the work for important intellectual content and assume responsibility for data integrity and the decision to submit this manuscript for publication; they had full access to the study data, edited and reviewed the manuscript drafts, and approved the final version for submission.
Acknowledgments: the authors thank the participating patients and their families, and the study centers and investigators for their contribu- tions to the study. We specially thank Professor Michel Attal from the
Thierry Facon, Adriań Alegre, Andrew Spencer,
Artur Jurczyszyn,6 Kazutaka Sunami,7 Laurent Frenzel,8 Chang-Ki Min,9 Sophie Guillonneau,10 Peggy L. Lin,11 Solenn Le-Guennec,12 Frank Campana,13
Helgi van de Velde,13 Samira Bensfia11 and Sara Bringhen14
1Oslo Myeloma Center, Oslo University Hospital and KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway; 2Dana-Farber Cancer Institute, Boston, MA, USA; 3Lille University Hospital, Lille, France; 4Hospital Universitario La Princesa & Hospital Quironsalud, Madrid, Spain; 5Department of Clinical Hematology, Alfred Health-Monash University, Melbourne, Australia; 6Department of Hematology, Jagiellonian University Medical College, Krakow, Poland; 7Department of Hematology, National Hospital Organization
Fredrik Schjesvold,1 Paul G. Richardson,2 345
haematologica | 2021; 106(4)