Risks of upper respiratory tract infection and pneumonia in patients with multiple myeloma receiving Daratumumab: A systematic review and meta-analysis of randomized controlled trials.

Ticona, Katy; Tun, Aung; Guevara, Elizabeth

doi:10.1200/jco.2018.36.15_suppl.e20005

Cited by 4 publications

(5 citation statements)

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“…The rate of pulmonary infections (13% grade 3-4) was similar to what has been observed with mAbs in MM. 28 High rates of grade 1 to 2 peripheral neuropathy were seen (41%), which was lower compared with Dara-VRd (63%, 7% grade 3-4). 9,22 Lenalidomide may be responsible for a significant portion of the observed neuropathy in this and other cited studies.…”

Section: Discussionmentioning

confidence: 80%

“…Significant cardiac events were rare; 1 patient died from a suspected (but not confirmed) myocardial infarction attributed to therapy. The rate of pulmonary infections (13% grade 3-4) was similar to what has been observed with mAbs in MM . High rates of grade 1 to 2 peripheral neuropathy were seen (41%), which was lower compared with Dara-VRd (63%, 7% grade 3-4) .…”

Section: Discussionmentioning

confidence: 99%

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Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent

et al. 2022

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IMPORTANCETreatment of newly diagnosed multiple myeloma (NDMM) with a quadruplet regimen consisting of a monoclonal antibody, proteasome inhibitor, immunomodulatory imide, and corticosteroid has been associated with improved progression-free survival (PFS) compared with triplet regimens. The optimal quadruplet combination, and whether this obviates the need for frontline autologous stem cell transplant (ASCT), remains unknown. We evaluated elotuzumab and weekly carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) without ASCT in NDMM.OBJECTIVE To investigate the efficacy of Elo-KRd using a measurable residual disease (MRD)-adapted design in NDMM regardless of ASCT eligibility. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, single-arm, phase 2 study enrolled patients between July 2017 and February 2021. Median follow-up was 29 months.INTERVENTIONS Twelve to 24 cycles of Elo-KRd; consecutive MRD-negative results at 10 −6 by next-generation sequencing (NGS) after cycles 8 (C8) and 12 determined the duration of Elo-KRd. This was followed by Elo-Rd (no carfilzomib) maintenance therapy until disease progression. MAIN OUTCOMES AND MEASURESThe primary end point was the rate of stringent complete response (sCR) and/or MRD-negativity (10 −5 ) after C8 Elo-KRd. Secondary end points included safety, rate of response, MRD status, PFS, and overall survival (OS). As an exploratory analysis, MRD was assessed using liquid chromatography mass spectrometry (MS) on peripheral blood samples. RESULTS Forty-six patients were enrolled (median age 62 years, 11 [24%] aged >70 years). Overall, 32 (70%) were White, 6 (13%) were Black, 3 (6%) were more than 1 race, and 5 (11%) were of unknown race. Thirty-three (72%) were men and 13 (28%) were women. High-risk cytogenetic abnormalities were present in 22 (48%) patients. The rate of sCR and/or MRD-negativity after C8 was 26 of 45 (58%), meeting the predefined statistical threshold for efficacy. Responses deepened over time, with the MRD-negativity (10 −5 ) rate increasing to 70% and MS-negativity rate increasing to 65%; concordance between MRD by NGS and MS increased over time. The most common (>10%) grade 3 or 4 adverse events were lung and nonpulmonary infections (13% and 11%, respectively). There was 1 grade 5 myocardial infarction. The estimated 3-year PFS was 72% overall and 92% for patients with MRD-negativity (10 −5 ) at C8. CONCLUSIONS AND RELEVANCEAn MRD-adapted design using elotuzumab and weekly KRd without ASCT showed a high rate of sCR and/or MRD-negativity and durable responses. This approach provides support for further evaluation of MRD-guided deescalation of therapy to decrease treatment exposure while sustaining deep responses.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent

et al. 2022

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“…Several other groups have reported similar findings of increased susceptibility to infectious complications of cytomegalovirus and fungal and parasitic infections among patients with myeloma receiving daratumumab. A recently published meta‐analysis designed to determine the risks of upper respiratory tract infections and pneumonia in patients with myeloma reported a pooled risk ratio for an upper respiratory tract infection of 1.59 (95% CI, 1.33‐1.91; P = .00001) and a pooled risk ratio for pneumonia of 1.48 (95% CI, 1.14‐1.93; P = .002) among patients receiving daratumumab . These findings warrant increased vigilance for infections among patients receiving daratumumab.…”

Section: Managing Daratumumab‐related Toxicities and Practical Aspectsmentioning

confidence: 98%

“…A recently published meta-analysis designed to determine the risks of upper respiratory tract infections and pneumonia in patients with myeloma reported a pooled risk ratio for an upper respiratory tract infection of 1.59 (95% CI, 1.33-1.91; P = .00001) and a pooled risk ratio for pneumonia of 1.48 (95% CI, 1.14-1.93; P = .002) among patients receiving daratumumab. 40 These findings warrant increased vigilance for infections among patients receiving daratumumab.…”

Section: Infection Risk With Daratumumabmentioning

confidence: 99%

Daratumumab in multiple myeloma

Nooka

Kaufman

Hofmeister

et al. 2019

Cancer

122

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The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.

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“…103 Results from trials with dara suggest that patients on combination regimens may be at elevated risk for varicella zoster virus infection and cytomegalovirus (CMV) reactivation. [103][104][105] Panel recommendations ► Patients should receive seasonal influenza vaccines while on isatuximab. ► To manage infections following treatment, IVIG should be administered according to established institutional criteria, which are not specific to isatuximab.…”

Section: Infection Carementioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

Shah

Aiello

Avigan

et al. 2020

J Immunother Cancer

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Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

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Risks of upper respiratory tract infection and pneumonia in patients with multiple myeloma receiving Daratumumab: A systematic review and meta-analysis of randomized controlled trials.

Cited by 4 publications

References 0 publications

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent

Daratumumab in multiple myeloma

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

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