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Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group
Nielsen, L. K., Schjesvold, F., Möller, S., Guldbrandsen, N., Hansson, M., Remes, K., Peceliunas, V., Abildgaard, N., Gregersen, H., King, M. T.
Journal of patient-reported outcomes. 2024;8(1):15
Abstract
BACKGROUND Decisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS). METHODS HRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P < 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum. RESULTS 168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8-5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1-5.9). CONCLUSIONS Kd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact.
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Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial
Dytfeld, D., Wróbel, T., Jamroziak, K., Kubicki, T., Robak, P., Walter-Croneck, A., Czyż, J., Tyczyńska, A., Druzd-Sitek, A., Giannopoulos, K., et al
The Lancet. Oncology. 2023
Abstract
BACKGROUND Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population. METHODS This study is an interim analysis of ATLAS, which is an investigator-initiated, multicentre, open-label, randomised, phase 3 trial in 12 academic and clinical centres in the USA and Poland. Participants were aged 18 years or older with newly diagnosed multiple myeloma, completed any type of induction and had stable disease or better, autologous stem-cell transplantation within 100 days, initiated induction 12 months before enrolment, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) using permuted blocks of sizes 4 and 6 and a web-based system to receive up to 36 cycles of carfilzomib, lenalidomide, and dexamethasone (28-day cycles of carfilzomib 20 mg/m(2) administered intravenously in cycle one on days 1 and 2 then 36 mg/m(2) on days 1, 2, 8, 9, 15, and 16 in cycles one to four and 36 mg/m(2) on days 1, 2, 15, and 16 from cycle five up to 36 [per protocol]; lenalidomide 25 mg administered orally on days 1-21; and dexamethasone 20 mg administered orally on days 1, 8, 15, and 22) or lenalidomide alone (10 mg administered orally for the first three cycles and then at the best tolerated dose [≤15 mg for 28 days in 28-day cycles]) until disease progression or unacceptable toxicity as maintenance therapy. After 36 cycles, patients in both treatment groups received lenalidomide maintenance. Randomisation was stratified by response to previous treatment, cytogenetic risk factors, and country. Investigators and patients were not masked to treatment allocation. Patients in the carfilzomib, lenalidomide, and dexamethasone group with no detectable minimal residual disease after cycle six (as per International Myeloma Working Group criteria) and standard-risk cytogenetics were switched to lenalidomide maintenance as of cycle nine. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all randomly assigned patients). Safety was analysed in all randomly assigned patients who received at least one dose of study treatment. This unplanned interim analysis was triggered by the occurrence of 59 (61%) of the expected 96 events for the primary analysis and the results are considered preliminary. This trial is registered with ClinicalTrials.gov, NCT02659293 (active, not recruiting) and EudraCT, 2015-002380-42. FINDINGS Between June 10, 2016, and Oct 21, 2020, 180 patients were randomly assigned to receive either carfilzomib, lenalidomide, and dexamethasone (n=93) or lenalidomide alone (n=87; intention-to-treat population). The median age of patients was 59·0 years (IQR 49·0-63·0); 84 (47%) patients were female and 96 (53%) were male. With a median follow-up of 33·8 months (IQR 20·9-42·9), median progression-free survival was 59·1 months (95% CI 54·8-not estimable) in the carfilzomib, lenalidomide, and dexamethasone group versus 41·4 months (33·2-65·4) in the lenalidomide group (hazard ratio 0·51 [95% CI 0·31-0·86]; p=0·012). The most common grade 3 and 4 adverse events were neutropenia (44 [48%] in the carfilzomib, lenalidomide, and dexamethasone group vs 52 [60%] in the lenalidomide group), thrombocytopenia (12 [13%] vs six [7%]), and lower respiratory tract infections (seven [8%] vs one [1%]). Serious adverse events were reported in 28 (30%) patients in the carfilzomib, lenalidomide, and dexamethasone group and 19 (22%) in the lenalidomide group. One treatment-related adverse event led to death (respiratory failure due to severe pneumonia) in the carfilzomib, lenalidomide, and dexamethasone group. INTERPRETATION This interim analysis provides support for considering carfilzomib, lenalidomide, and dexamethasone therapy in patients with newly diagnosed multiple myeloma who completed any induction regimen followed by autologous stem-cell transplantation, which requires confirmation after longer follow-up of this ongoing phase 3 trial. FUNDING Amgen and Celgene (Bristol Myers Squibb).
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Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial
Kubicki, T., Dytfeld, D., Wróbel, T., Jamroziak, K., Robak, P., Czyż, J., Tyczyńska, A., Druzd-Sitek, A., Giannopoulos, K., Szczepaniak, T., et al
British journal of haematology. 2023
Abstract
Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B-cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard-risk patients with minimal residual disease negativity after six cycles de-escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de-escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B-cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression-free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.
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Adjuvanted recombinant zoster vaccine decreases herpes zoster-associated pain and the use of pain medication across 3 randomized, placebo-controlled trials
Kim, J. H., Johnson, R., Kovac, M., Cunningham, A. L., Amakrane, M., Sullivan, K. M., Dagnew, A. F., Curran, D., Schuind, A.
Pain. 2023;164(4):741-748
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Abstract
Herpes zoster (HZ) and HZ-associated pain greatly affect patients' quality of life, particularly in older and immunocompromised adults, for whom comorbidities and polypharmacy are often reported. Three phase III, randomized, placebo-controlled clinical trials have reported the adjuvanted recombinant zoster vaccine (RZV) as highly efficacious in preventing HZ and reducing pain severity in healthy adults ≥50 years old (Zoster Efficacy Study [ZOE]-50 study, NCT01165177) and ≥70 years old (ZOE-70; NCT01165229) and in immunocompromised adults ≥18 years old undergoing autologous hematopoietic stem cell transplantation (ZOE-HSCT; NCT01610414). Here, we investigated efficacy of RZV in reducing (i) the duration of clinically significant pain (Zoster Brief Pain Inventory pain score ≥3) and (ii) HZ-associated pain medication use and duration of use in participants with confirmed HZ ("breakthrough cases") from the 3 studies. Recombinant zoster vaccine effectively reduced the duration of clinically significant HZ-associated pain during HZ episodes by 38.5% ( P -value: 0.010) in the ZOE-HSCT study. Although a similar trend was observed in the ZOE-50 and ZOE-70 studies, the results were not statistically significant because of the high vaccine efficacy (VE) against HZ resulting in rare breakthrough cases. VE in reducing pain medication use (39.6%; P -value: 0.008) and duration of medication use (49.3%, P -value: 0.040) was reported in the ZOE-70 study; corresponding positive VE estimates were observed in the ZOE-50 and ZOE-HSCT studies but were not statistically significant. Data reported here demonstrate efficacy of RZV in reducing HZ-associated pain duration and pain medication use in breakthrough cases, thereby improving quality of life of those with HZ.
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Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the FIL MCL0208 trial
Ferrero, S., Grimaldi, D., Arrigoni, E., Pironti, M., Zaccaria, G. M., Alessandria, B., Genuardi, E., De Luca, G., Ghislieri, M., Tavarozzi, R., et al
Blood advances. 2023
Abstract
In the FIL MCL0208 phase III trial, lenalidomide maintenance (LEN) after transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabolic enzymes, or cell surface receptors might predict drug efficacy. Genotypes were obtained by real-time polymerase chain reaction (RT-PCR) in peripheral blood (PB) germ line DNA. Polymorphisms of either ABCB1 or VEGF were found in 69% and 79% of 278 patients and predicted favorable PFS vs homozygous wild type (WT) in the LEN arm: 3-year PFS 85% vs 70% (p < 0.05) and 85% vs 60% (p < 0.01), respectively. Patients carrying both ABCB1 and VEGF WT had the poorest 3-year PFS (46%) and overall survival (OS, 76%): in fact, in these patients LEN did not improve PFS vs OBS (3-year PFS 44% vs 60%, p = 0.62). Moreover, CRBN polymorphism (n = 28) was associated with lenalidomide dose reduction or discontinuation. Finally, ABCB1, NCF4, and GSTP1 polymorphisms predicted lower hematological toxicity during induction, while ABCB1 and CRBN polymorphisms predicted lower risk of grade ≥3 infections. This study demonstrates that specific SNPs represent candidate predictive biomarkers of immunochemotherapy toxicity and LEN efficacy after ASCT in MCL. This trial is registered at eudract.ema.europa.eu as 2009-012807-25.
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Lenalidomide and dexamethasone with or without ixazomib maintenance tailored by residual disease status in myeloma
Rosiñol, L., Oriol, A., Ríos-Tamayo, R., Blanchard, M. J., Jarque, I., Bargay, J., Hernandez Garcia, M. T., Cabañas, V., Carrillo-Cruz, E., Sureda, A., et al
Blood. 2023
Abstract
From November 2014 to May 2017, 332 patients homogeneously treated with VRD induction, ASCT and VRD consolidation were randomized to receive maintenance therapy with RD (161 patients) vs IRD (171 patients). RD consisted of lenalidomide 15 mg/d from days 1-21 plus dexamethasone 20 mg/d on days 1-4 and 9-12 at 4-weeks intervals while in the IRD arm oral ixazomib at a dose of 4 mg on days 1,8, and 15 was added. MRD negative patients after 24 cycles were discontinued while those who were MRD positive remained on maintenance with RD for 36 more cycles. The MRD negativity from baseline increased from 50.9% to 71.8% with RD and from 59.6% to 72.4% with IRD at 2 years. After a median follow-up of 69 months from the initiation of maintenance, the PFS was similar in both arms, median not reached in either arm with a 6-years PFS rate of 61.3% and 55.6% for RD and IRD, respectively (HR 1.136 [95% CI 0.809 - 1.603]). No significant differences in PFS between RD and IRD were observed in any prognostic subgroup. After 2 years of maintenance, treatment was discontinued in 163 patients who were MRD negative while 63 MRD positive patients were continued on RD therapy. Maintenance discontinuation in MRD negative patients resulted in a low progression rate (17.2% at 4 years), even in patients with high-risk features. In summary, our results show the efficacy of RD maintenance and support the safety of maintenance discontinuation in MRD negative patients at 2 years. This trial is registered at ClinicalTrials.gov (NCT02406144) and EudraCT (2014-00055410).
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Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial
Xuan, L., Wang, Y., Yang, K., Shao, R., Huang, F., Fan, Z., Chi, P., Xu, Y., Xu, N., Deng, L., et al
The Lancet. Haematology. 2023
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Editor's Choice
Abstract
BACKGROUND Our open-label, multicentre, randomised, phase 3 trial showed that sorafenib maintenance after haematopoietic stem-cell transplantation (HSCT) improved overall survival and reduced relapse for patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic HSCT. Here, we present a post-hoc analysis on the 5-year follow-up data of this trial. METHODS This phase 3 trial, done in seven hospitals in China, included patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT, who were aged 18-60 years, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days after transplantation. Patients were randomly assigned (1:1) to receive sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days after transplantation. Randomisation was done with permuted blocks (block size four) via an interactive web-based system. Investigators and participants were not masked to group assignment. The primary endpoint was the 1-year cumulative incidence of relapse, which was reported previously. For this updated analysis, the 5-year endpoints were overall survival; cumulative incidence of relapse; non-relapse mortality; leukaemia-free survival; graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS); cumulative incidence of chronic GVHD; and late effects in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT02474290, and is complete. FINDINGS Between June 20, 2015, and July 21, 2018, 202 patients were randomly assigned to sorafenib maintenance (n=100) or non-maintenance (n=102). Median follow-up was 60·4 months (IQR 16·7-73·3). Extended follow-up showed improved overall survival (72·0% [95% CI 62·1-79·7] vs 55·9% [45·7-64·9]; hazard ratio [HR] 0·55, 95% CI 0·34-0·88; p=0·011), leukaemia-free survival (70·0% [60·0-78·0] vs 49·0% [39·0-58·3]; 0·47, 0·30-0·73; p=0·0007), and GRFS (58·0% [47·7-67·0] vs 39·2% [29·8-48·5]; 0·56, 0·38-0·83; p=0·0030), lower cumulative incidence of relapse (15·0% [8·8-22·7] vs 36·3% [27·0-45·6]; 0·33, 0·18-0·60; p=0·0003), and no increase in non-relapse mortality (15·0% [8·8-22·7] vs 14·7% [8·6-22·3]; 0·79, 0·39-1·62; p=0·98) for patients in the sorafenib group compared with those in the control group. The 5-year cumulative incidence of chronic GVHD (54·0% [43·7-63·2] vs 51·0% [40·8-60·3]; 0·82, 0·56-1·19; p=0·73) did not differ significantly between the two groups and we did not find substantial differences in late effects between the two groups. There were no treatment-related deaths. INTERPRETATION With extended follow-up, sorafenib maintenance after transplantation is associated with improved long-term survival and reduced relapse rates compared with non-maintenance, further supporting this strategy as a standard of care for patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT. FUNDING None. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
PICO Summary
Population
Adults up to 60 years with FLT3-ITD acute myeloid leukaemia in composite remission before and after transplantation, recruited from seven centres in China (n=202)
Intervention
Sorafenib (400 mg orally twice daily) maintenance (n=100)
Comparison
Control: Non-maintenance (n=102)
Outcome
Median follow-up was 60·4 months (IQR 16·7-73·3). Extended follow-up showed improved overall survival (72·0% [95% CI 62·1-79·7] vs 55·9% [45·7-64·9]; hazard ratio [HR] 0·55, 95% CI 0·34-0·88), leukaemia-free survival (70·0% [60·0-78·0] vs 49·0% [39·0-58·3]; 0·47, 0·30-0·73), and GvHD-free-relapse-free survival (58·0% [47·7-67·0] vs 39·2% [29·8-48·5]; 0·56, 0·38-0·83), lower cumulative incidence of relapse (15·0% [8·8-22·7] vs 36·3% [27·0-45·6]; 0·33, 0·18-0·60), and no increase in non-relapse mortality (15·0% [8·8-22·7] vs 14·7% [8·6-22·3]; 0·79, 0·39-1·62) for patients in the sorafenib group compared with those in the control group. The 5-year cumulative incidence of chronic GVHD (54·0% [43·7-63·2] vs 51·0% [40·8-60·3]; 0·82, 0·56-1·19) did not differ significantly between the two groups and we did not find substantial differences in late effects between the two groups. There were no treatment-related deaths.
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Exposure-Response Analyses of Letermovir Following Oral and Intravenous Administration in Allogeneic Hematopoietic Cell Transplantation Recipients
Prohn, M., Cho, C. R., Viberg, A., Dykstra, K., Davis, C., Sabato, P., Stone, J., Badshah, C., Murata, Y., Leavitt, R., et al
Clinical Pharmacology and Therapeutics. 2022;111(2):485-495
Abstract
The cytomegalovirus (CMV) viral terminase inhibitor letermovir is approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplantation recipients. In a phase III trial (NCT02137772), letermovir significantly reduced clinically significant CMV infection (CS-CMVi) rate vs. placebo through Week 24 (primary end point) and Week 14 (secondary end point) post transplantation. Here, exposure-response relationships were investigated using efficacy and selected safety end points from the phase III trial to inform the proposed clinical dose. Post hoc exposure estimates were derived from a population pharmacokinetic model. No significant exposure dependencies were found for CS-CMVi through Week 24 or Week 14 among letermovir-treated participants. Evaluated covariates had no impact on exposure-efficacy relationships and letermovir plasma exposure did not affect time of CS-CMVi onset. There was no dependence between adverse event incidence and letermovir exposure. These results support current dosing recommendations in several countries and regions, including the United States and European Union.
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Multicenter phase II, double-blind placebo-controlled trial of maintenance ixazomib after allogeneic transplantation for high-risk multiple myeloma: Results of the BMT CTN 1302 Trial
Bashir, Q., Nishihori, T., Pasquini, M. C., Martens, M. J., Wu, J., Alsina, M., Anasetti, C., Brunstein, C., Dawson, P., Efebera, Y., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND The role of allogeneic hematopoietic cell transplantation (allo-HCT) followed by maintenance therapy in high-risk multiple myeloma remains controversial. We evaluated the efficacy of ixazomib maintenance therapy after a reduced-intensity allo-HCT from HLA-matched donors in patients with high-risk multiple myeloma. OBJECTIVES The primary endpoint for this study was progression-free survival (PFS) post-randomization, treated as a time to event. Secondary endpoints were grades 2-4 and 3-4 acute graft-versus-host-disease (GVHD), chronic GVHD, best response, disease progression, non-relapse mortality (NRM), overall survival (OS), toxicity, infection, and health-related quality of life (HRQOL). STUDY DESIGN In this phase 2, double-blinded, prospective multicenter trial, we randomized patients with high-risk multiple myeloma (poor-risk cytogenetics, plasma cell leukemia, or relapsing within 24 months after autologous transplant) to ixazomib (3 mg, days 1, 8, 15) or a placebo after allo-HCT. The conditioning regimen included fludarabine/melphalan/bortezomib with tacrolimus plus methotrexate for GVHD. RESULTS Fifty-seven patients were enrolled. 52 (91.2%) received allo-HCT, and 43 (82.7%) were randomized to ixazomib vs. placebo. At 21-month post-randomization, ixazomib vs. placebo groups had similar PFS (55.3% vs. 59.1%, p=1.00) and OS (94.7% vs. 86.4%, p=0.17). Cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% vs. 0%) and chronic GVHD at 12 months (68.6% vs. 63.6%) were similar. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OS were 52% and 82%, respectively, with corresponding non-relapse mortality of 11.7%. CONCLUSIONS These results show the safety and durable disease control with allo-HCT in high-risk myeloma patients. We could not adequately assess the efficacy of ixazomib maintenance as the trial terminated early because of enrollment delays, but there was no signal of an impact on outcomes.
PICO Summary
Population
People with high-risk myeloma from 15 centres in USA (n=57)
Intervention
Allogeneic transplant with ixazomib maintenance therapy (n=21)
Comparison
Allogeneic transplant with placebo (n=22); not randomised (n=14)
Outcome
At 21-month post-randomisation, ixazomib vs. placebo groups had similar PFS (55.3% vs. 59.1%) and OS (94.7% vs. 86.4%). Cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% vs. 0%) and chronic GVHD at 12 months (68.6% vs. 63.6%) were similar. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OS were 52% and 82%, respectively, with corresponding non-relapse mortality of 11.7%.
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AFM13 in patients with relapsed or refractory classical Hodgkin lymphoma: final results of an open-label, randomized, multicenter phase II trial
Sasse, S., Bröckelmann, P. J., Momotow, J., Plütschow, A., Hüttmann, A., Basara, N., Koenecke, C., Martin, S., Bentz, M., Grosse-Thie, C., et al
Leukemia & lymphoma. 2022;:1-8
Abstract
In patients with relapse of classical Hodgkin lymphoma (cHL) after autologous stem cell transplant, brentuximab vedotin and anti-PD1 treatment, the outcome is poor. To assess the efficacy of the bispecific anti-CD30/CD16A, NK-cell engaging antibody AFM13 and to select the optimal treatment schedule (arm A-C), we initiated a randomized two-stage phase II trial (NCT02321592). Due to slow recruitment, the trial was terminated after treatment of 25 patients. Treatment with AFM13 was well tolerated: only two treatment-associated serious adverse events (SAEs) were reported; all SAEs resolved completely. With an objective response rate (ORR) of 16.7% (1/5 in arm A, 1/11 in arm B, and 2/8 in arm C) and a 12-month progression-free survival (PFS) of 12.6% (95% CI 3.2-28.9), treatment efficacy of AFM13 monotherapy in all evaluable patients was modest. The continuous application schedule (arm C) might be more effective, but the visit schedule should be better aligned with patients' daily life.