P-180: Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in newly diagnosed Multiple Myeloma (NDMM): analysis of vascular thrombotic events (VTEs) in the GRIFFIN study

Sborov, Douglas W.; Baljevic, Muhamed; Reeves, Brandi; Laubach, Jacob P.; Efebera, Yvonne A.; Rodriguez, Cesar; Costa, Luciano J.; Chari, Ajai; Silbermann, Rebecca; Holstein, Sarah A.; Anderson, Larry D.; Kaufman, Jonathan L.; Shah, Nina; Pei, Huiling; Pate, Sharmila; Cortoos, Annelore; Bartlett, Blake; Vermeulen, Jessica; Lin, Thomas S.; Voorhees, Peter M.; Richardson, Paul G.

doi:10.1016/s2152-2650(21)02307-7

Cited by 4 publications

(24 citation statements)

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“…9 Similarly, the addi tion of daratu mumab to lenalidomidebortezomibdexa meth a sone (RVd; phase 2 GRIFFIN trial) in trans planteli gi ble patients improved depth of response, includ ing strin gent com plete remis sion and min i mal resid ual dis ease (MRD) (10 −5 ), and showed PFS benefit (HR 0.45; p = 0.324), while median OS was not reached in either group with limited followup. 10 In both CASSIOPEIA and GRIFFIN, there was a ben e fit to adding daratumumab across all sub groups except those with highrisk cyto ge net ics or International Scoring System stage III dis ease. A PFS ben e fit is also seen for front line daratumamab in com bi na tion with bortezomibmel pha lanpred ni sone (VMP; phase 3 ALCYONE trial) or lenalidomidedexa meth a sone (Rd; phase 3 MAIA trial) in trans plantinel i gi ble patients.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Antibodies and bispecifics for multiple myeloma: effective effector therapy

2022

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The therapeutic landscape in multiple myeloma (MM) has changed dramatically over the last 2 decades. With the introduction of novel immunotherapies, patients with MM can expect deeper responses, longer remissions, and improved overall survival. Since its approval by the US Food and Drug Administration in 2015, the monoclonal antibody specific for CD38, daratumumab, has been incorporated into both frontline and relapsed treatment regimens. Its role as a maintenance therapy is currently being explored. Subsequently, a variety of novel antibody therapeutics have evolved from the success of daratumumab, using similar concepts to target the malignant plasma cell clone. Noteworthy naked monoclonal antibodies include isatuximab, another agent directed against CD38, and elotuzumab, an agent directed against SLAM family member 7. Antibody-drug conjugates, complex molecules composed of an antibody tethered to a cytotoxic drug, target malignant cells and deliver a lethal payload. The first to market is belantamab mafodotin, which targets B-cell maturation antigen (BCMA) on malignant plasma cells and delivers a potent microtubule inhibitor, monomethyl auristatin F. Additionally, bispecific T-cell antibodies are in development that engage the immune system directly by simultaneously binding CD3 on T cells and a target epitope—such as BCMA, G-protein coupled receptor family C group 5 member D (GPRC5d), and Fc receptor homologue 5 (FcRH5)—on malignant cells. Currently, teclistamab, an anti-BCMA bispecific, is closest to approval for commercial use. In this review, we explore the evolving landscape of antibodies in the treatment of MM, including their role in frontline and relapse settings.

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Section: Monoclonal Antibodiesmentioning

confidence: 99%

Antibodies and bispecifics for multiple myeloma: effective effector therapy

2022

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“…PROSPECT: A Study Whose Time Is Past F irst of all, kudos to Deb Schrag, MD, MPH, and all the investigators of the phase 2/3 PROSPECT trial (NCT01515787) for achieving and completing this landmark study. 1 In appreciating its signi cance, it is helpful to turn back the hands of time to the 1980s. At this time the Gastrointestinal Tumor Study Group performed a 4-arm randomized study in adjuvant therapy of rectal cancer, showing for the rst time that both radiation and chemotherapy were better than surgery alone but that the combination of both had the best outcome.…”

Section: Our Board Members Have Been Busy! Take a Look To See What Th...mentioning

confidence: 99%

Erdheim-Chester Disease: A Case Report of BRAF V600E–Negative, MAP2K1-Positive ECD Diagnosed by Blood Next-Generation Sequencing Assay and a Brief Literature Review

2023

Oncology

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INDICATIONS AND USAGERYBREVANT is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1) in Full Prescribing Information], whose disease has progressed on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14) in Full Prescribing Information]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. CONTRAINDICATIONSNone. WARNINGS AND PRECAUTIONS Infusion-Related ReactionsRYBREVANT can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. Based on the safety population [see Adverse Reactions], IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR. Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended [see Dosage and Administration (2.3) in Full Prescribing Information]. Administer RYBREVANT via a peripheral line on Week 1 and Week 2 [see Dosage and Administration (2.6) in Full Prescribing Information]. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity [see Dosage and Administration (2.4) in Full Prescribing Information]. Interstitial Lung Disease/Pneumonitis RYBREVANT can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population [see Adverse Reactions], ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT due to ILD/pneumonitis. Monitor patients for new or worsening symptoms indicative of ILD/ pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed [see Dosage and Administration (2.4) in Full Prescribing Information]. Dermatologic Adverse ReactionsRYBREVANT can cause rash (including dermatitis acneiform), pruritus and dry skin. Based on the s...

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“…Other agents with anti-myeloma activity, such as the monoclonal antibodies, daratumumab, belantamab and elotuzumab, and the oral proteasome inhibitor ixazomib, have not been associated with an increased risk of thrombotic complications [ 67 , 68 , 69 , 70 ], at least in the clinical trial setting. In the GRIFFIN study, daratumumab with VRD (DVRd) was compared to VRd, and the all-grade cumulative rates of VTE were 10% and 15%, respectively [ 73 ]. A post-hoc pooled analysis of the phase III CASTOR, POLLUX and MAIA trials demonstrated that daratumumab treatment did not affect VTE risk [ 78 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…The SAVED scores were calculated retrospectively in the GRIFFIN study for patients in both the Dara-VRd and VRd arms. Median SAVED scores in both groups were in the low-risk category (0 and 0.5 scores, respectively); the VTE risk was low, but the incidence of VTE in both groups was relatively high [ 73 ]. In addition, only 60% of patients in the Dara-RVd and 67% in the RVd arm were on antithrombotic treatment at the time of VTE [ 73 ].…”

Section: Literature Reviewmentioning

confidence: 99%

“…Median SAVED scores in both groups were in the low-risk category (0 and 0.5 scores, respectively); the VTE risk was low, but the incidence of VTE in both groups was relatively high [ 73 ]. In addition, only 60% of patients in the Dara-RVd and 67% in the RVd arm were on antithrombotic treatment at the time of VTE [ 73 ]. The performances of the SAVED and IMPEDE-VTE risk scores were retrospectively assessed in the CASTOR, POLLUX and MAIA studies; both scores had good discrimination for patients on non-daratumumab-based regimens, and the SAVED score performed better in patients receiving daratumumab [ 78 ].…”

Section: Literature Reviewmentioning

confidence: 99%

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Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma

Fotiou

Dimopoulos

2022

Cancers

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Multiple myeloma (MM) is associated with an increased risk of thrombotic complications, which remains substantial despite the implementation of thromboprophylaxis. The procoagulant state that characterizes the disease is multifactorial, and a greater understanding of the underlying pathophysiology is required to inform appropriate thrombosis prevention. Currently, there is a shift towards using direct oral anticoagulants (DOACs) in this setting; head-to-head comparisons in the context of controlled clinical trials between class agents are still missing. MM-specific VTE risk assessment scores have been developed to optimize management and minimize the associated mortality/morbidity. Their clinical utility remains to be evaluated. The value of adding biomarkers to clinical scores to optimize their performance and increase their discriminatory power is also under assessment.

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P-180: Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in newly diagnosed Multiple Myeloma (NDMM): analysis of vascular thrombotic events (VTEs) in the GRIFFIN study

Cited by 4 publications

References 0 publications

Antibodies and bispecifics for multiple myeloma: effective effector therapy

Antibodies and bispecifics for multiple myeloma: effective effector therapy

Erdheim-Chester Disease: A Case Report of BRAF V600E–Negative, MAP2K1-Positive ECD Diagnosed by Blood Next-Generation Sequencing Assay and a Brief Literature Review

Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma

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