Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study
Abstract Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is currently approved for relapsed-refractory multiple myeloma....
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-03-01
|
| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-023-00816-8 |
| _version_ | 1827979564592136192 |
|---|---|
| author | Fen Saj Yadav Nisha Prasanth Ganesan Smita Kayal Rakhee Kar Dhanapathi Halanaik Biswajit Dubashi |
| author_facet | Fen Saj Yadav Nisha Prasanth Ganesan Smita Kayal Rakhee Kar Dhanapathi Halanaik Biswajit Dubashi |
| author_sort | Fen Saj |
| collection | DOAJ |
| description | Abstract Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is currently approved for relapsed-refractory multiple myeloma. This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of bortezomib, pomalidomide, and dexamethasone (VPd) induction for NDMM. We used Fleming’s two-stage design for sample size calculation. We included transplant-eligible and ineligible patients aged 18–75 years in the study. The patients received four cycles of VPd induction followed by response assessment. Thirty-four patients were included in the study, of which 31 completed all four cycles of induction. The median age was 52 years (32–72). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had ISS-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Three patients had high-risk cytogenetic abnormalities. After four cycles of VPd induction, ten patients (32%) achieved stringent CR, nine had CR (29%), eight (26%) had VGPR, and 4 (13%) had PR. Fifteen (48%) had a complete metabolic response (CMR) on PET-CT. Two patients developed SAEs. Anemia was the most common hematological toxicity. Peripheral neuropathy and constipation were the most common non-hematological toxicities. Patients with ≥VGPR had significantly better 12-month PFS than those with PR. Patients with ≥VGPR and CMR on PET-CT had significantly better 12-month OS. Our study showed VPd induction is safe and efficacious in NDMM. Further Phase 3 studies are necessary to establish the superiority and survival benefits. |
| first_indexed | 2024-04-09T21:38:43Z |
| format | Article |
| id | doaj.art-247ba0f75d0747059a6addcd4a179b44 |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-09T21:38:43Z |
| publishDate | 2023-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-247ba0f75d0747059a6addcd4a179b442023-03-26T11:06:56ZengNature Publishing GroupBlood Cancer Journal2044-53852023-03-011311610.1038/s41408-023-00816-8Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II StudyFen Saj0Yadav Nisha1Prasanth Ganesan2Smita Kayal3Rakhee Kar4Dhanapathi Halanaik5Biswajit Dubashi6Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)Department of PathologyDepartment of Nuclear MedicineDepartment of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)Abstract Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is currently approved for relapsed-refractory multiple myeloma. This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of bortezomib, pomalidomide, and dexamethasone (VPd) induction for NDMM. We used Fleming’s two-stage design for sample size calculation. We included transplant-eligible and ineligible patients aged 18–75 years in the study. The patients received four cycles of VPd induction followed by response assessment. Thirty-four patients were included in the study, of which 31 completed all four cycles of induction. The median age was 52 years (32–72). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had ISS-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Three patients had high-risk cytogenetic abnormalities. After four cycles of VPd induction, ten patients (32%) achieved stringent CR, nine had CR (29%), eight (26%) had VGPR, and 4 (13%) had PR. Fifteen (48%) had a complete metabolic response (CMR) on PET-CT. Two patients developed SAEs. Anemia was the most common hematological toxicity. Peripheral neuropathy and constipation were the most common non-hematological toxicities. Patients with ≥VGPR had significantly better 12-month PFS than those with PR. Patients with ≥VGPR and CMR on PET-CT had significantly better 12-month OS. Our study showed VPd induction is safe and efficacious in NDMM. Further Phase 3 studies are necessary to establish the superiority and survival benefits.https://doi.org/10.1038/s41408-023-00816-8 |
| spellingShingle | Fen Saj Yadav Nisha Prasanth Ganesan Smita Kayal Rakhee Kar Dhanapathi Halanaik Biswajit Dubashi Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study Blood Cancer Journal |
| title | Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study |
| title_full | Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study |
| title_fullStr | Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study |
| title_full_unstemmed | Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study |
| title_short | Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study |
| title_sort | efficacy and safety of pomalidomide bortezomib and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma pomace phase ii study |
| url | https://doi.org/10.1038/s41408-023-00816-8 |
| work_keys_str_mv | AT fensaj efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy AT yadavnisha efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy AT prasanthganesan efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy AT smitakayal efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy AT rakheekar efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy AT dhanapathihalanaik efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy AT biswajitdubashi efficacyandsafetyofpomalidomidebortezomibanddexamethasonecombinationchemotherapyfornewlydiagnosedmultiplemyelomapomacephaseiistudy |