Outcomes of VD-PACE With Immunomodulatory Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

Abdallah, Al‐Ola; Sigle, Monia; Mohyuddin, Ghulam Rehman; Coggins, Emily; Remker, Cassie; Shune, Leyla; Mahmoudjafari, Zahra; McGuirk, Joseph P.; Ganguly, Siddhartha

doi:10.1016/j.clml.2020.09.002

Cited by 8 publications

(9 citation statements)

References 27 publications

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“…With the failure of modern treatment options, and most recent developments such as bispecific antibodies and CAR-T-cell therapies not yet widely available, classic chemotherapy combination regimens like the VTd-PACE regimen and its modifications may be beneficial in these situations. By investigating the clinical course of 31 heavily pretreated patients with r/r MM receiving VTd-PACE and PACE-M as salvage therapy, we observed an ORR of 71% which is in line with previously reported ORR of 67.7%, 68.4%, 73%, 75%, and 77% [8,10,11,26,27] and is significantly higher than the lately described ORR of 20% to the next applied therapy for triple-class exposed patients [4]. Usually, complete responses only account for a minor part of the ORR reported for VTd-PACE or PACE-M with 0-14% [7-11, 13, 27-29].…”

Section: Discussionsupporting

confidence: 91%

“…By investigating the clinical course of 31 heavily pretreated patients with r/r MM receiving VTd-PACE and PACE-M as salvage therapy, we observed an ORR of 71% which is in line with previously reported ORR of 67.7%, 68.4%, 73%, 75%, and 77% [ 8 , 10 , 11 , 26 , 27 ] and is significantly higher than the lately described ORR of 20% to the next applied therapy for triple-class exposed patients [ 4 ]. Usually, complete responses only account for a minor part of the ORR reported for VTd-PACE or PACE-M with 0–14% [ 7 – 11 , 13 , 27 – 29 ]. Thus, we do not consider the lack of complete responses in our study population as unusual, as bone marrow evaluations for response documentation were not performed routinely in clinical practice, but see our results in line with previously reported data of most retrospective studies [ 5 , 7 , 9 , 12 , 13 , 28 ].…”

Section: Discussionsupporting

confidence: 91%

“…With the failure of modern treatment options, classic chemotherapy combinations like the VTd-PACE regimen, a combination of bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide, and its modifications (PACE-M) are used as salvage therapy. However, systematic data of those regimens in the era of novel agents are rare [5][6][7][8][9][10][11][12][13]. Initially, the efficacy of PACEbased regimes was not only used for patients with relapsed or refractory (r/r) MM, but also investigated in patients with newly diagnosed MM.…”

Section: Introductionmentioning

confidence: 99%

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VTd-PACE and VTd-PACE-like regimens are effective salvage therapies in difficult-to-treat relapsed/refractory multiple myeloma: a single-center experience

Ghandili

Alihodzic²,

Wiessner³

et al. 2022

Ann Hematol

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Although treatment options for multiple myeloma (MM) are rapidly evolving, there still remain difficult-to-treat situations, especially in relapsed and/or refractory (r/r) disease. When modern therapies are exhausted, or emergency treatment is needed for high tumor burden, classic chemotherapy combination regimens like the VTd-PACE regimen and its modifications (PACE-M) may also be beneficial as bridging to subsequent treatment options. This single-center retrospective analysis aimed to investigate the outcome of VTd-PACE and PACE-M salvage therapy in 31 heavily pretreated r/r MM patients. The primary objective was the overall response rate (ORR). Secondary objectives were median progression-free survival (mPFS), median overall survival (mOS), safety, and renal response. Median age was 59 years (range 39–75), and 71% of patients were male. R-ISS stratification showed high-risk MM in 48%. The median number of prior therapies was 3, with 23 patients being triple- and 12 penta-refractory (74% and 39%). ORR was 71%, including 23% of patients achieving a very good partial response. Median duration of follow-up was 15 months (range 0–29 months). mPFS and mOS were 3 months (95% CI 0.27–5.74) and 11 months (95% CI 3.66–18.35), respectively. In 26 patients (83.9%), at least one subsequent treatment (stem cell transplant or BCMA-directed) was administered. Renal function significantly improved after VTd-PACE or PACE-M treatment (p = 0.032). Non-hematological adverse events ≥ grade 3 were predominantly infections. VTd-PACE and PACE-M are effective salvage therapies in difficult-to-treat situations in heavily pre-treated r/r MM, including patients with impaired renal function. VTd-PACE and PACE-M can be successfully used as bridging therapy for subsequent treatment.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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VTd-PACE and VTd-PACE-like regimens are effective salvage therapies in difficult-to-treat relapsed/refractory multiple myeloma: a single-center experience

Ghandili

Alihodzic²,

Wiessner³

et al. 2022

Ann Hematol

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“…Cytotoxic agents containing chemotherapy including ASCT might be effective for EMD [ 79 , 198 , 199 ]. VTD-PACE is a good option for EMD considering CAM-DR and hypoxia, but might be intolerable for the majority of patients with a terminal phase of MM [ 200 ].…”

Section: Overall Treatment Strategy Considering Microenvironment Amentioning

confidence: 99%

Treatment Strategies Considering Micro-Environment and Clonal Evolution in Multiple Myeloma

Suzuki

Nishiwaki

Yano

2021

Cancers

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Multiple myeloma is an uncurable hematological malignancy because of obtained drug resistance. Microenvironment and clonal evolution induce myeloma cells to develop de novo and acquired drug resistance, respectively. Cell adhesion-mediated drug resistance, which is induced by the interaction between myeloma and bone marrow stromal cells, and soluble factor-mediated drug resistance, which is induced by cytokines and growth factors, are two types of de novo drug resistance. The microenvironment, including conditions such as hypoxia, vascular and endosteal niches, contributes toward de novo drug resistance. Clonal evolution was associated with acquired drug resistance and classified as branching, linear, and neutral evolutions. The branching evolution is dependent on the microenvironment and escape of immunological surveillance while the linear and neutral evolution is independent of the microenvironment and associated with aggressive recurrence and poor prognosis. Proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibody agents (MoAbs), and autologous stem cell transplantation (ASCT) have improved prognosis of myeloma via improvement of the microenvironment. The initial treatment plays the most important role considering de novo and acquired drug resistance and should contain PIs, IMIDs, MoAb and ASCT. This review summarizes the role of anti-myeloma agents for microenvironment and clonal evolution and treatment strategies to overcome drug resistance.

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“…The regimen VDPACE + IMiD consisted of high‐dose dexamethasone (40 mg on days 1–4) and a 4‐day continuous infusion of cisplatin 10 mg/m 2 , cyclophosphamide 40 mg/m 2 , etoposide 40 mg/m 2 , doxorubicin 10 mg/m 2 , and bortezomib 1 mg/m 2 on days 1, 4, 8, and 11 in addition to an IMiD (thalidomide or lenalidomide) administered every 4 to 6 weeks (Table 2 ) [ 26 , 27 ]. All patients received lenalidomide except two patient who received thalidomide due to cytopenia.…”

Section: Treatment Protocolmentioning

confidence: 99%

Outcomes of VDPACE with an immunomodulatory agent as a salvage therapy in relapsed/refractory multiple myeloma with extramedullary disease

Abdallah

Mohyuddin

Ahmed

et al. 2021

eJHaem

Self Cite

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Extramedullary disease (EMD) is an aggressive form of multiple myeloma (MM). Confirming the presence of plasma cells outside the bone marrow makes the diagnosis of EMD. There is no clear consensus on the management of EMD in MM, and this entity continues to remain an unmet need. Rapidly controlling EMD to prevent end‐organ damage is a priority. Retrospectively, we reviewed our database for patients with EMD that received treatment with bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide (VDPACE) plus an immune modulator (IMiD) regimen. We identified 21 patients with a median age of 61 years. Ten patients received a VDPACE based regimen as a bridge to autologus stem cell transplant (ASCT). After a median follow‐up of 51.4 months, the median overall survival (OS) and progression‐free survival were 14.9 months (95% CI: 7.8‐NA) and 5.5 months (95% CI: 3.9‐NA), respectively. The overall response rate was 76%, with a manageable safety profile. Interestingly, these results were similar regardless of the presence of high‐risk cytogenetics. The safety profile was acceptable. In conclusion, a salvage VDPACE‐based regimen plus an IMiD remains an effective and safe bridging therapy to future ASCT and immunotherapy in relapsed/refractory multiple myeloma patients with EMD.

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Outcomes of VD-PACE With Immunomodulatory Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

Cited by 8 publications

References 27 publications

VTd-PACE and VTd-PACE-like regimens are effective salvage therapies in difficult-to-treat relapsed/refractory multiple myeloma: a single-center experience

VTd-PACE and VTd-PACE-like regimens are effective salvage therapies in difficult-to-treat relapsed/refractory multiple myeloma: a single-center experience

Treatment Strategies Considering Micro-Environment and Clonal Evolution in Multiple Myeloma

Outcomes of VDPACE with an immunomodulatory agent as a salvage therapy in relapsed/refractory multiple myeloma with extramedullary disease

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