Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease

Zhou, Xiang; Flüchter, Patricia; Nickel, Katharina; Meckel, Katharina; Messerschmidt, Janin; Böckle, David; Knorz, Sebastian; Steinhardt, Maximilian; Krummenast, Franziska; Danhof, Sophia; Einsele, Hermann; Kortüm, K. Martin; Rasche, Leo

doi:10.3390/cancers12041035

Cited by 32 publications

(22 citation statements)

References 47 publications

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“…Also, progression of plasmacytomas despite good BM and serological response in patients receiving thalidomide has been reported 88–90,92 . These phenomena have also been observed with bortezomib 83 and carfilzomib 85 …”

Section: Treatment Approachmentioning

confidence: 83%

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Expert review on soft‐tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations

et al. 2021

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In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1Á7% to 4Á5% and 7% to 34Á4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

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Section: Treatment Approachmentioning

confidence: 83%

“…Bortezomib seems to be of benefit in patients with PS disease with less evidence for EMD involvement 81–83 . Carfilzomib showed limited efficacy in relapsed patients with MM and plasmacytomas, particularly in those with EMD disease 84,85 . The efficacy of ixazomib is unknown.…”

Section: Treatment Approachmentioning

confidence: 99%

Expert review on soft‐tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations

et al. 2021

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“…So erzielt die Induktionstherapie mit dem CD38-gerichteten Antikörper Daratumumab in Vierfachkombination mit Bortezomib, Dexamethason und Thalidomid bzw. Lenalidomid ein progressionsfreies Überleben ("progression free survival" [PFS]) von über 90 % nach 18 [1] bzw. 24 Monaten [2].…”

Section: Status Quo Und Therapeutische Herausforderungen Beim Multiplen Myelomunclassified

CAR-T-Zell-Therapie beim multiplen Myelom

2021

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ZusammenfassungDie Behandlung mit CAR-T-Zellen (CAR chimärer Antigenrezeptor) ist eine neuartige Strategie der zellulären Immuntherapie, die das patienteneigene Immunsystem als „Waffe gegen Tumorzellen“ benutzt. Bei Patienten mit multiplem Myelom werden CAR-T-Zell-Therapien im Rahmen klinischer Studien getestet. Die aktuellen Studiendaten der gegen das „B-cell maturation antigen“ (BCMA) gerichteten CAR-T-Zell-Therapien zeigen eine beachtliche Wirksamkeit, die eine baldige Zulassung erwarten lässt. Allerdings erleiden weiterhin die meisten Patienten nach einer Behandlung mit CAR-T-Zellen ein Rezidiv. Hinzu kommt, dass CAR-T-Zell-Therapien zu schwerwiegenden Nebenwirkungen wie Zytokinfreisetzungssyndrom und Neurotoxizität mit teilweise auch letalem Ausgang führen können. Ein angemessenes Kosten-Nutzen-Verhältnis der CAR-T-Zell-Therapie stellt eine weitere Herausforderung dar. Trotz dieser Limitationen erscheint die CAR-T-Zell-Therapie eine attraktive Option für Patienten mit Myelom, sodass diese Therapie das Potenzial hat, in die Standardbehandlung integriert zu werden.

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“…A recent updated meta-analysis of 20 studies demonstrated a pooled ORR of 84% with 43% complete remission (CR) in patients with heavily pretreated RRMM who had received BCMA directed CAR T cell (10). Importantly, even the heavily pretreated patients with extramedullary disease (EMD), a high risk feature, presented a high ORR of 78%, which could not be achieved by conventional combination chemotherapies such as "VDT-PACE" (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) (34), "DexaBEAM" (dexamethasone, carmustine, etoposide, cytarabine, and melphalan) (35), daratumumab (36) or carfilzomib containing treatments (37). However, as reported by Gagelmann et al, synthesized results of five full publications from China or the United States (38-42) yielded a relapse rate of 45% at the last follow up, and the median progressionfree survival (PFS) was only 10 months (10).…”

Section: Overview Of Car T Cell Therapy For Multiple Myelomamentioning

confidence: 99%

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies

et al. 2020

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In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their “last chance” and a “hope of cure”. However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.

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Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease

Cited by 32 publications

References 47 publications

Expert review on soft‐tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations

Expert review on soft‐tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations

CAR-T-Zell-Therapie beim multiplen Myelom

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies

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