DCEP and bendamustine/prednisone as salvage therapy for quad- and penta-refractory multiple myeloma

Goldsmith, Scott; Fiala, Mark A.; Wang, Brandon; Schroeder, Mark A.; Wildes, Tanya M.; Ghobadi, Armin; Stockerl-Goldstein, Keith; Vij, Ravi

doi:10.1007/s00277-020-03970-2

Cited by 14 publications

(11 citation statements)

References 46 publications

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“…However, CC is gradually being side-lined due to the better risk/benefit ratio of the new combinations [ 130 ]. Bridging therapy (when cytoreduction is urgently needed before more definitive therapy is planned) is one of the most common indications for CC, especially in certain circumstances, such as aggressive extramedullary disease or secondary plasma cell leukemia [ 131 ].…”

Section: Controversies Surrounding the Clinical Management Of Patients With Rrmmmentioning

confidence: 99%

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

et al. 2022

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The increase in the number of therapeutic alternatives for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM) patients has widened the clinical scenario, leading to a level of complexity that no algorithm has been able to cover up to date. At present, this complexity increases due to the wide variety of clinical situations found in MM patients before they reach the status of relapsed/refractory disease. These different backgrounds may include primary refractoriness, early relapse after completion of first-line therapy with latest-generation agents, or very late relapse after chemotherapy or autologous transplantation. It is also important to bear in mind that many patient profiles are not fully represented in the main randomized clinical trials (RCT), and this further complicates treatment decision-making. In RRMM patients, the choice of previously unused drugs and the number and duration of previous therapeutic regimens until progression has a greater impact on treatment efficacy than the adverse biological characteristics of MM itself. In addition to proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and corticosteroids, a new generation of drugs such as XPO inhibitors, BCL-2 inhibitors, new alkylators and, above all, immunotherapy based on conjugated anti-BCMA antibodies and CAR-T cells, have been developed to fight RRMM. This comprehensive review addresses the fundamentals and controversies regarding RRMM, and discusses the main aspects of management and treatment. The basis for the clinical management of RRMM (complexity of clinical scenarios, key factors to consider before choosing an appropriate treatment, or when to treat), the arsenal of new drugs with no cross resistance with previously administered standard first line regimens (main phase 3 clinical trials), the future outlook including the usefulness of abandoned resources, together with the controversies surrounding the clinical management of RRMM patients will be reviewed in detail.

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Section: Controversies Surrounding the Clinical Management Of Patients With Rrmmmentioning

confidence: 99%

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

et al. 2022

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“…To date, the therapy of late‐stage aggressive RRMM remains challenging. Patients with penta‐refractory MM, particularly, have very poor outcome 22,23 . In this study, we retrospectively evaluated data of patients with heavily pretreated high‐risk RRMM that was treated with “Dara‐KDT‐P(A)CE” and its modifications.…”

Section: Discussionmentioning

confidence: 99%

Salvage therapy with “Dara‐KDT‐P(A)CE” in heavily pretreated, high‐risk, proliferative, relapsed/refractory multiple myeloma

Zhou

Ruckdeschel

Peter

et al. 2021

Hematological Oncology

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The multi-agent therapy "VDT-PACE" represents an established regimen in relapsed/refractory multiple myeloma (RRMM). Here, we report on our experience with a "modified VDT-PACE" incorporating new generation anti-MM agents daratumumab and carfilzomib ("Dara-KDT-P(A)CE"). We retrospectively analyzed 38 patients with RRMM treated with "Dara-KDT-P(A)CE". The median age was 62 (range 45-82) years, and the patients were heavily pretreated with a median of 5 (range 2-12) prior lines of therapy. Twenty-one (55%) patients suffered from pentarefractory MM. High-risk cytogenetics was present in 31 (81%) patients. The patients received a median of 2 (range 1-10) cycles of this therapy, and the overall response rate (ORR) was 70%. Patients with penta-refractory MM and high-risk cytogenetics showed similar ORR of 65% and 79%, respectively. The median progression-free survival (PFS) and overall survival were 4.1 (95% CI 2.7-5.4) and 8.4 (95% CI 6.7-10.0) months, respectively. Patients with lactate dehydrogenase >250 IU/L showed significantly shorter PFS in comparison with others patients (p = 0.006). We used this regimen as bridging therapy prior to chimeric antigen receptor T-cell infusion in four patients. In conclusion, "Dara-KDT-P(A)CE" is an effective salvage therapy for patients with heavily pretreated, multi-refractory, high-risk RRMM lacking alternative options.

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“…Combined, these factors provide a rationale for the use of alkylator‐based combined chemotherapy in TCR MM, yet evidence is scarce. Regimens deployed in this setting include variations of VDT‐PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide), 36 HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), 37 DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin), 38 and single‐agent bendamustine, 38 among others. In the Mammoth study, 80 patients received cytotoxic chemotherapy as next line after development of TCR.…”

Section: Treatment Optionsmentioning

confidence: 99%

“…We believe that given the dismal prognosis of TCR MM, the lack of a clearly superior and widely available therapy, and the absence of high-level evidence in this setting, it is imperative to offer such patients enrolment in therapeutic clinical trials whenever possible. Here we summarise clinical data on different drugs, combinations and approaches (Table 1) [35][36][37][38][39][40][41][42][43][44][45][46] employed in this setting and suggest an algorithm to guide choice of therapy (Figure 1).…”

Section: Tr E Atm E N T Op Tionsmentioning

confidence: 99%

How I treat triple‐class refractory multiple myeloma

et al. 2022

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Immunomodulatory imide drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (MoAbs) are the pillars of modern multiple myeloma (MM) therapy. The prognosis of patients with MM that became refractory to these three classes (triple-class refractory [TCR]) is historically poor. Observational studies indicate an overall response rate of ~30% and overall survival inferior to 1 year with existing therapies. While no randomised trial has been completed in this setting, several agents exploring new mechanisms of action showed activity in TCR MM in single-arm trials, including anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cells, anti-BCMA antibody-drug conjugates and exportin 1 (XPO1) inhibitors. Among agents in development, anti-BCMA bispecific T-cell engagers (TCE), and non-BCMA TCEs demonstrated activity in most patients. Additionally, specific agents may exhibit unique activity in biologically defined patient subsets, as exemplified by venetoclax in t(11;14) MM. The main open questions in TCR MM are preferred sequence of existing therapies, the utility of sequential use of agents with similar mechanism of action, but different immunotherapy target and the relative efficacy of the different anti-BCMA platforms. Here, we summarise the existing literature and provide general guidance on selecting therapy for this challenging and heterogenous group of patients.

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DCEP and bendamustine/prednisone as salvage therapy for quad- and penta-refractory multiple myeloma

Cited by 14 publications

References 46 publications

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies

Salvage therapy with “Dara‐KDT‐P(A)CE” in heavily pretreated, high‐risk, proliferative, relapsed/refractory multiple myeloma

How I treat triple‐class refractory multiple myeloma

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