A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma

Joseph R Mikhael, Paul Richardson, Saad Z. Usmani, Noopur Raje, William Bensinger, Chatchada Karanes, Frank Campana, Dheepak Kanagavel, Franck Dubin, Qianying Liu, Dorothée Semiond, Kenneth Anderson

Research output: Contribution to journalArticle

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Abstract

This phase 1b dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly for 4 weeks, followed by every 2 weeks), pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg (weekly) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n = 8], 10 [n = 31], or 20 [n = 6] mg/kg). Patients received a median of 3 (range, 1-10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 patients (42%) remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 treatment-emergent adverse event was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pretreated patients with RRMM. The 10 mg/kg weekly/every 2 weeks isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov as #NCT02283775.

Original languageEnglish (US)
Pages (from-to)123-133
Number of pages11
JournalBlood
Volume134
Issue number2
DOIs
StatePublished - Jul 11 2019

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Multiple Myeloma
Refractory materials
Dexamethasone
Proteasome Inhibitors
Pharmacokinetics
Safety
Toxicity
Lymphopenia
Leukopenia
Therapeutics
pomalidomide
Neutropenia
Fatigue of materials
Respiratory Tract Infections
Thrombocytopenia
Dyspnea
Disease-Free Survival
Fatigue
Anemia
Pneumonia

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Mikhael, J. R., Richardson, P., Usmani, S. Z., Raje, N., Bensinger, W., Karanes, C., ... Anderson, K. (2019). A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Blood, 134(2), 123-133. https://doi.org/10.1182/blood-2019-02-895193

A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. / Mikhael, Joseph R; Richardson, Paul; Usmani, Saad Z.; Raje, Noopur; Bensinger, William; Karanes, Chatchada; Campana, Frank; Kanagavel, Dheepak; Dubin, Franck; Liu, Qianying; Semiond, Dorothée; Anderson, Kenneth.

In: Blood, Vol. 134, No. 2, 11.07.2019, p. 123-133.

Research output: Contribution to journalArticle

Mikhael, JR, Richardson, P, Usmani, SZ, Raje, N, Bensinger, W, Karanes, C, Campana, F, Kanagavel, D, Dubin, F, Liu, Q, Semiond, D & Anderson, K 2019, 'A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma', Blood, vol. 134, no. 2, pp. 123-133. https://doi.org/10.1182/blood-2019-02-895193
Mikhael JR, Richardson P, Usmani SZ, Raje N, Bensinger W, Karanes C et al. A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Blood. 2019 Jul 11;134(2):123-133. https://doi.org/10.1182/blood-2019-02-895193
Mikhael, Joseph R ; Richardson, Paul ; Usmani, Saad Z. ; Raje, Noopur ; Bensinger, William ; Karanes, Chatchada ; Campana, Frank ; Kanagavel, Dheepak ; Dubin, Franck ; Liu, Qianying ; Semiond, Dorothée ; Anderson, Kenneth. / A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. In: Blood. 2019 ; Vol. 134, No. 2. pp. 123-133.
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abstract = "This phase 1b dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly for 4 weeks, followed by every 2 weeks), pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg (weekly) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n = 8], 10 [n = 31], or 20 [n = 6] mg/kg). Patients received a median of 3 (range, 1-10) prior lines; most were refractory to their last regimen (91{\%}), with 82{\%} lenalidomide-refractory and 84{\%} PI-refractory. Median treatment duration was 9.6 months; 19 patients (42{\%}) remain on treatment. Most common adverse events included fatigue (62{\%}), and upper respiratory tract infection (42{\%}), infusion reactions (42{\%}), and dyspnea (40{\%}). The most common grade ≥3 treatment-emergent adverse event was pneumonia, which occurred in 8 patients (17.8{\%}). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98{\%} each; neutropenia, 93{\%}; and thrombocytopenia, 84{\%}). Overall response rate was 62{\%}; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pretreated patients with RRMM. The 10 mg/kg weekly/every 2 weeks isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov as #NCT02283775.",
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