Impact of anti-CD38 therapy in multiple myeloma with high-risk cytogenetics: systematic review and meta-analysis

Mohyuddin, Ghulam Rehman; Sigle, Monia; Chandrasekar, Viveksandeep Thoguluva; Aziz, Muhammad; Abdallah, Al‐Ola; Shune, Leyla; McClune, Brian

doi:10.1080/10428194.2020.1772475

Cited by 7 publications

(10 citation statements)

References 15 publications

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“…They observed an increased PFS in RRMM patients with daratumumab; however, they did not reveal benefit of that agent in high genetic risk NDMM 11 . Similarly to that publication, the findings of two other studies could not support the survival benefit of daratumumab in high cytogenetic risk NDMM 12 , 13 .…”

Section: Introductionmentioning

confidence: 84%

“…Secondly, although all meta-analyses used the random effect model, the weights of the included studies slightly differ among the meta-analyses regarding this analysis. It has to be noted that the meta-analysis of Mohyuddin et al did not reveal PFS benefit of adding daratumumab in high cytogenetic risk NDMM 13 ; however that study did not use the HRs provided by the original publication and recalculated them from raw data. This resulted HRs that differed much from the ones calculated by the studies included.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

Kiss

Gede

Hegyi

et al. 2021

Sci Rep

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Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33–5.61)] and sCR [OR = 2.29 (CI 1.49–3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39–0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76–10.66)] and sCR [OR = 3.08 (CI 2.00–4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37–0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

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Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

Kiss

Gede

Hegyi

et al. 2021

Sci Rep

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“…In TE NDMM, CASSIOPEIA 9 and GRIFFIN 21 studies demonstrated a higher stringent complete response (CR) and MRD negativity rates with the addition of D to bortezomib, thalidomide, and dexamethasone (VTD) and bortezomib, lenalidomide (len), and dexamethasone (RVd), respectively. 8,9 While D-based quadruplet regimens consistently induce deeper responses and higher MRD negativity, overall survival (OS) at current follow-up remains similar and the benefit in high-risk MM subsets is not clear. [21][22][23][24][25] Achievement of MRD negativity, however, is recognized as a robust predictor of longer remissions and is an acceptable early practical surrogate end point.…”

Section: Moab-based Quadrupletsmentioning

confidence: 99%

Immunotherapy in Multiple Myeloma—Time for a Second Major Paradigm Shift

Mohan

Hari

Dhakal

2021

JCO Oncology Practice

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Multiple myeloma (MM) is a genetically heterogenous disease and remains mostly incurable with a small group of patients achieving long-term disease remission. The past decade witnessed enormous efforts to break the circulus vitiosus of tumor-induced immunosuppression and to re-engage the immune system to fight cancer. The first-in-class anti-CD38 monoclonal antibody, daratumumab, has shown unprecedented responses especially in combination with other novel agents in both newly diagnosed and relapsed MM. There has been great interest in harnessing the power of T cells with bispecific antibodies and chimeric antigen receptor T-cell therapies in hematologic malignancies including MM. These immune-based approaches have shown notable antimyeloma effects with deeper, durable responses in early clinical trials of heavily pretreated patients with MM with limited therapeutic options. Several trials are underway investigating both single and combinatorial immune therapies at different stages with a hope to bring major transformation in MM. In the current review, we summarize how an immunologic approach offers promise for the treatment of MM and is setting the stage for second major paradigm shift 2 decades after the emergence of thalidomide and novel therapeutics.

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“…This study showed a similar median PFS of 33.64 in VRd (control arm) versus 31.47 in Elo-VRd (study arm) at a 53-month follow-up [ 33 ]. The GMMG HD6 phase III trial (ClinicalTrials.gov Identifier: NCT02495922) is currently investigating the role of Elo in combination with VRd induction/consolidation and lenalidomide maintenance within an autologous stem cell transplant-based approach [ 34 ]. While the preliminary results after four cycles of induction therapy, showed that the ORR and VGPR rates for the VRd plus Elo group as compared with the VRd group were 82% versus 86%, and 58% versus 54%, respectively, the final results are much awaited.…”

Section: Monoclonal Antibodies Are Increasing Becoming An Important Part Of Upfront Therapymentioning

confidence: 99%

“…The manageable toxicity profile and robust clinical efficacy of moAbs allow the combination with existing standard of care regimens in transplant and ineligible patients with NDMM. The efficacy of moAb based regimens in newly diagnosed high-risk MM remains to be confirmed in randomized clinical trials [ 20 , 34 , 36 ] and the identification of distinct subsets of patients (i.e., high stage/high-risk disease, TIE) who will specifically benefit from quadruple versus triplet therapy needs to be elucidated to further help clinicians in their decision making. Further clinical trials that intend to answer some of these clinical questions are already recruiting: the EQUATE trial randomizes NDMM patients without intent for upfront ASCT to a quadruple D-VRd versus DRd consolidation followed by DRd maintenance (ClinicalTrials.gov Identifier: NCT04566328).…”

Section: Monoclonal Antibodies Are Increasing Becoming An Important Part Of Upfront Therapymentioning

confidence: 99%

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma

Mohan

Maatman

Schinke

2021

Cancers

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Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients [1]. Over the past decade, we have witnessed the “era of monoclonal antibody (moAb)”, setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal outcome. Emerging T-cell directing therapies, such as bispecific antibody (bsAb) and chimeric antigen receptor T cells (CAR T) have shown unprecedented responses and outcomes in these heavily pretreated and treatment-refractory patients. Their clinical efficacy combined with high tolerability will likely lead to the use of these agents earlier in the treatment course and there is great enthusiasm that a combination of T cell directed therapy with moAbs can lead to long duration remission in the near future, possibly even without the need of high dose chemotherapy and stem cell transplantation. Herein, we summarize the role of naked moAbs in MM in the context of newer immunotherapeutic agents like bsAb and CAR T therapy.

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Impact of anti-CD38 therapy in multiple myeloma with high-risk cytogenetics: systematic review and meta-analysis

Cited by 7 publications

References 15 publications

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials

Immunotherapy in Multiple Myeloma—Time for a Second Major Paradigm Shift

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma

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