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Radiation Therapy Can Be Safely Incorporated into Pretransplantation Treatment Regimens for Patients with Multiple Myeloma
Damron, E. P., Qazilbash, M. H., Fang, P. Q., Wu, S. Y., Dabaja, B. S., Rondon, G., Hosing, C., Champlin, R. E., Bashir, Q., Shpall, E. J., et al
Transplantation and cellular therapy. 2023;29(1):37.e1-37.e7
Abstract
Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 10(6) CD34(+)/kg PBPCs (range, .5 to 54.8× 10(6) CD34(+)/kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 10(6) CD34(+)/kg PBPCs, and 166 (83%) collected >5.0 × 10(6) CD34(+)/kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.
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Phase 1 study of the combination of escalated total marrow irradiation using helical Tomotherapy and fixed high-dose melphalan (140 mg/m²) followed by autologous stem cell transplantation at first relapse in multiple myeloma
Cailleteau, A., Maingon, P., Choquet, S., Bourdais, R., Antoni, D., Lioure, B., Hulin, C., Batard, S., Llagostera, C., Guimas, V., et al
International journal of radiation oncology, biology, physics. 2022
Abstract
PURPOSE A second intensification is an option at first relapse in multiple myeloma (MM) after more than 36 months of initial remission. Many conditioning regimens have been tested, with or without total body irradiation (TBI). Recently, it was found that TBI could be replaced by total marrow irradiation (TMI) using helical Tomotherapy with promising results. METHODS AND MATERIALS This study was a prospective multicenter phase 1 trial which aimed to determine the maximum tolerated dose (MTD) of TMI administered in association with melphalan 140 mg/m², followed by autologous stem cell transplantation (ASCT) as consolidation at first relapse in MM. Four dose levels were explored: 8 Gy, 10 Gy, 12 Gy, and 14 Gy. The dose-limiting toxicity (DLT) was defined as: grade 4 neutropenia > 15 days, grade 4 thrombopenia > 28 days, and all other grade 4 non-hematologic toxicities except nausea, vomiting, alopecia, mucositis, and reaction to autologous stem cell infusion. RESULTS Thirteen patients were included: only one DLT at the third escalated dose level (12 Gy) was observed, whereas one patient was treated at 14 Gy with no adverse event. The MTD was not reached. The rate of acute toxicity was low: 38% of grade 3/4 diarrhea, mucositis, or unexplained fever. Regarding the lungs, the mean dose administered was systematically less than 8 Gy. After a median follow-up of 55 months, 70% of participants were alive. Of the 13 patients, 38.5% were in very good partial response (VGPR) and 30.8% in complete response (CR). Three of them were progression-free. Six patients were long survivors, still alive after 55 months of follow-up. CONCLUSION TMI provides good results with a good tolerance profile at first relapse in MM. TMI makes it possible to increase the dose delivered to the PTV while sparing organs at risk (OAR). This technique could be discussed for all regimens before auto- or allo-stem cell rescue when TBI is required.
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Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma
Giebel, S., Sobczyk-Kruszelnicka, M., Blamek, S., Saduś-Wojciechowska, M., Najda, J., Czerw, T., Mendrek, W., Woźniak, G., Jochymek, B., Radwan, M., et al
Bone marrow transplantation. 2021;56(6):1297-1304
Abstract
The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m(2) for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.
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4.
Radiation Therapy can be Safely Incorporated Into Pre-Transplant Treatment Regimens for Patients With Multiple Myeloma
Damron, E. P., Qazilbash, M., Fang, P., Wu, S. Y., Dabaja, B., Rondon, G., Hosing, C., Champlin, R., Bashir, Q., Shpall, E. J., et al
International journal of radiation oncology, biology, physics. 2021;111(3s):S81
Abstract
PURPOSE/OBJECTIVE(S): Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplant (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. We retrospectively examined the possible effect of RT on PBPC collection. MATERIALS/METHODS We reviewed the charts of 732 MM patients (pts) seen from 1997-2016 at our institution and included pts who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage (%) bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlations and t-tests. RESULTS Of 732 MM pts, ASCT was planned for 485 pts; of these, 223 pts received RT prior to PBPC collection and were included in the final cohort. 133 pts (60%) were male. Median age at PBPC collection was 59 years (range 33-80). For SIT, pts received combination regimens including the following agents: bortezomib (142 pts, 64%); lenalidomide (111 pts, 50%); alkylators (46 pts, 21%). Nine pts (4%) received dexamethasone alone. RT plans and/or a description of the fields, were available to estimate treated BM% for 221 pts. The median cumulative BM% treated per pt was 6.7 (range 0.0-47.4). The median RT dose was 24 Gy (range 10.0-75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 pts, 85%), G-CSF with plerixafor (15 pts, 7%), or chemotherapy (19 pts, 8%). PBPC collection data was available for 199 pts. A median of 7.8?×?10(6) CD34(+)/kg PBPCs (range 0.5-54.8) were collected in a median of 3 (1-9) apheresis procedures. 196 pts (99%) collected more than 2.0?×?10(6) CD34(+)/kg (minimum PBPC no. required for engraftment), and 167 pts (84%) collected more than 5.0?×?10(6) CD34(+)/kg (preferred no. of PBPCs collected). The number of PBPCs collected was not associated with BM% treated (P?=?0.15) or RT dose (P?=?0.56). The number of apheresis procedures performed was not associated with BM% treated (P?=?0.54) or RT dose (P?=?0.85). The number of PBPCs collected did not differ significantly for pts receiving RT to the pelvis (P?=?0.96), lumbar spine (P?=?0.35), or thoracic spine (P?=?0.059). Time to platelet engraftment was longer for patients with higher %BM treated (P?=?0.02). Eleven pts did not undergo a confirmed ASCT due to: pt preference (3 pts), trial therapy (1 pt), comorbidities (1 pt), election for hospice (1 pt), inadequate collection (4 pts) and inadequate follow up (1 pt). CONCLUSION Among pts with MM, RT prior to ASCT did not prevent adequate PBPC collection or impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.