Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials

Weisel, Katja; Májer, István; Oriol, Albert; Goldschmidt, Hartmut; Ludwig, Heinz; Campioni, Marco; Szabó, Zsolt; Dimopoulos, Meletios A.

doi:10.1080/10428194.2019.1648806

Cited by 6 publications

(6 citation statements)

References 29 publications

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“…The safety profile across the dose levels was similar to that of other contemporary relapsed regimens. 15,[25][26][27][28] PK results demonstrated that carfilzomib exposure adjusted for body surface area was similar between adults and children and across different age groups of children, at least for patients 1 year of age and above. A limited set of proteasome inhibition data indicated that proteasome activity in peripheral blood was completely suppressed 2 hours after the first target dose of carfilzomib at doses of 36 mg/m 2 and higher, and remained at least partially suppressed compared to baseline, on day 29 of induction.…”

Section: Discussionmentioning

confidence: 99%

Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia

Burke

Ziegler

Bautista

et al. 2022

Pediatric Blood & Cancer

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Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in childhood. Survival for patients following relapse remains poor, and achieving complete remission (CR) after relapse is the first critical step to cure. Carfilzomib is a proteasome inhibitor with an acceptable safety profile and clinical activity in adults with multiple myeloma but has not been assessed in children. The primary objective of this phase 1b study was to assess the safety and tolerability of carfilzomib combined with vincristine, dexamethasone, asparaginase, and daunorubicin (VXLD) in children with relapsed and/or refractory ALL.Methods: Patients aged 1-21 years (n = 24) received 4-week induction therapy with carfilzomib at dose levels of 27 mg/m 2 (n = 3), 36 mg/m 2 (n = 7), 45 mg/m 2 (n = 4), and 56 mg/m 2 (n = 10) in combination with VXLD. Patients achieving stable disease

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Section: Discussionmentioning

confidence: 99%

Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia

Burke

Ziegler

Bautista

et al. 2022

Pediatric Blood & Cancer

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“…The outcome of patients with MM has significantly improved over the past decade due to novel therapeutic agents such as proteasome inhibitors, immunomodulatory drugs, mAbs, and autologous stem cell transplantation [ 70 ]. Nevertheless, despite high treatment efficacy, most of the patients eventually relapse, with a short progression-free survival period [ 71 , 72 , 73 ]. In the particular case of the clinically approved mAb Daratumumab, the pharmacological effect is due to the direct induction of apoptosis, ADCC, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Selection, Expansion, and Unique Pretreatment of Allogeneic Human Natural Killer Cells with Anti-CD38 Monoclonal Antibody for Efficient Multiple Myeloma Treatment

Motais

Charvátová

Walek

et al. 2021

Cells

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Cellular immunotherapy is becoming a new pillar in cancer treatment after recent striking results in different clinical trials with chimeric antigen receptor T cells. However, this innovative therapy is not exempt from challenges such as off-tumor toxicity, tumor recurrence in heterogeneous tumors, and affordability. To surpass these limitations, we exploit the unique anti-tumor characteristics of natural killer (NK) cells. In this study, we aimed to obtain a clinically relevant number of allogeneic NK cells derived from peripheral blood (median of 14,050 million cells from a single donor) to target a broad spectrum of solid and liquid tumor types. To boost their anti-tumor activity, we combined allogeneic NK cells with the approved anti-cluster of differentiation 38 (CD-38) monoclonal antibody Daratumumab to obtain a synergistic therapeutic effect against incurable multiple myeloma. The combination therapy was refined with CD16 polymorphism donor selection and uncomplicated novel in vitro pretreatment to avoid undesired fratricide, increasing the in vitro therapeutic effect against the CD-38 positive multiple myeloma cell line by more than 20%. Time-lapse imaging of mice with established human multiple myeloma xenografts revealed that combination therapy of selected and pretreated NK cells with Daratumumab presented tumor volumes 43-fold smaller than control ones. Combination therapy with an allogeneic source of fully functional NK cells could be beneficial in future clinical settings to circumvent monoclonal antibodies’ low therapeutic efficiency due to NK cell dysfunctionality in MM patients.

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“…Examining outcomes after prior lenalidomide exposure, the median PFS in CASTOR Daratumumab, bortezomib and dexamethasone arm (DVd) was 7.8 months (lenalidomide refractory) – 21.2 months (prior lenalidomide exposure and receiving DVd in 2nd line). Data specifically in patients getting DVd after relapse on LM is not reported 27‐32 . However, in all the trials listed above, data examining the regimens specifically in relapse after LM are lacking.…”

Section: Discussionmentioning

confidence: 99%

The impact of lenalidomide maintenance on second‐line chemotherapy in transplant eligible patients with multiple myeloma

Cherniawsky

Kukreti

Reece

et al. 2021

European J of Haematology

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Objectives To understand the impact of therapy sequencing on progression‐free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low‐dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting. Methods We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second‐line therapy, 575 patients were included. Results Patients treated with LM had statistically similar 2nd PFS when re‐exposed to lenalidomide in second‐line therapy compared to those receiving non‐lenalidomide‐containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second‐line therapy than their non‐LM counterparts. Conclusion Our data suggest that patients progressing on LM who receive lenalidomide‐containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non‐lenalidomide‐containing second‐line regimens. Identification of patients mostly likely to benefit from further lenalidomide‐containing therapy is paramount.

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Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials

Abstract: Dimopoulos (2020) Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and

Cited by 6 publications

References 29 publications

Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia

Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia

Selection, Expansion, and Unique Pretreatment of Allogeneic Human Natural Killer Cells with Anti-CD38 Monoclonal Antibody for Efficient Multiple Myeloma Treatment

The impact of lenalidomide maintenance on second‐line chemotherapy in transplant eligible patients with multiple myeloma

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