Transplant-eligible Patients Research Articles

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients. In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m2 subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m2 orally; and prednisone 60 mg/m2 orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression. After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%). D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www. gov as #NCT03217812.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: There is currently no consensus on the role of upfront ASCT for patients with T cell Non-Hodgkin lymphomas (T-NHL), especially in patients who have achieved complete remission (CR1) following induction chemotherapy. To date, no randomized control trials (RCTs) exist and available data is conflicting, especially with regards to T-NHL subtypes that might benefit. A systematic review and meta-analysis of all comparative studies (randomized, non-randomized and observational) was hence performed to address this question. Methods: A comprehensive, systematic search (from 1/2000 to 2/2022) of MEDLINE/PubMed, EMBASE and Cochrane databases was performed. PRISMA and Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Studies were screened based on predefined inclusion/exclusion criteria, and were critically appraised for outcomes of interest [progression free survival (PFS) and overall survival (OS)]. Quality of studies was assessed using Newcastle-Ottawa Scale. Hazard ratios (HRs) and corresponding 95% Cis were calculated, and the meta-analysis was performed using the random-effects model. Test for heterogeneity was performed using I2 statistic. Results: Of 3297 unique records, 17 studies (prospective = 6, retrospective = 11) were included. Median follow up in these studies ranged from 22 to 94 mths. Ten studies compared upfront ASCT versus No ASCT in patients with complete remission (CR1), while in 7 patients achieving either PR1 (first partial remission) or CR1 were included[MS1]. Of these, 9 studies included only transplant eligible patients. The T-NHL subtypes included in the studies were also heterogenous, with nodal T-NHLs, in particular Angioimmunoblastic T-NHL (AITL) being amongst the most common subtypes. Results: from the meta-analysis showed that PFS in T-NHL patients who underwent ASCT benefited (HR 0.64, 95% CI: 0.46–0.89, I2 = 74%) compared to not undergoing ASCT; however similar benefit was not observed in OS (HR 0.67, 95% CI: 0.36–1.23, I2 = 89%). Sensitivity analyses including only studies with patients transplanted in CR1, and studies involving transplant eligible patients showed similar findings. In the studies that evaluated patients with the AITL subtype, ASCT showed a significant benefit in PFS and OS, compared to not undergoing ASCT (PFS = HR 0.19, 95% CI: 0.11–0.32, I2 20%; OS = HR 0.27, 95% CI: 0.09–0.81, I2 88 (Figure 1). Keyword: stem cell transplant No conflicts of interests pertinent to the abstract.

Safety and clinical activity of belantamab mafodotin plus lenalidomide and dexamethasone in transplant ineligible patients with newly diagnosed multiple myeloma: The phase 1/2, prospective, open-label, BelaRd study.

8050 Background: We present the updated safety and efficacy of upfront belantamab mafodotin (belamaf) plus lenalidomide and dexamethasone (Rd) in transplant ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM). Methods: The ongoing, prospective, open-label, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 pts with TI NDMM, with ECOG PS &lt; 2 and adequate organ function. In Part 1, 36 pts are randomized (1:1:1) to receive belamaf 2.5, 1.9, or 1.4 mg/kg Q8W plus Rd. Eye exams include Snellen best corrected visual acuity (BCVA) and corneal exam (slit lamp examination). Ocular adverse evets (OAEs) are classified by CTCAE v5.0. This descriptive analysis presents the updated safety and efficacy findings for all Part 1 pts (cutoff date 15/12/22). Results: The analysis included 36 pts [median age: 73 years (64–86); male: 19 (53%)], of whom 31 (86%) were still on treatment and 5 (14%) had discontinued [4 pts due to belamaf-unrelated adverse events (AEs); 1 pt withdrew consent]. At baseline, 32 (89%) pts were intermediate fit as per International Myeloma Working Group frailty score and 34 (94%) had ECOG PS≤1. Median follow up was 15 months (3–23); median belamaf administrations and number of cycles reached were 6 (2–10) and 15 (3–22). Thirty-four (94%) pts experienced ≥1 grade (Gr) ≥3 treatment-emergent AEs (TEAEs). Most common (≥ 10% of pts) non ocular Gr ≥3 TEAEs were fatigue (21 pts, 58%), rash (6 pts, 17%), diarrhoea (5 pts, 14%) and COVID-19 infection (4 pts, 11%); no Gr ≥3 thrombocytopenias and any Gr infusion-related reactions were reported. Regarding pts visual acuity, out of a total of 499 BCVA assessments, 164 (33%) were Gr 2 and 54 (11%) were Gr 3. Notably, a meaningful BCVA decline (worse than 20/50 in better seeing eye) was observed in 38 (8%) assessments, with a median time to resolution of 1 month. Regarding clinically relevant Gr≥2 ocular symptoms, blurred vision, dry eye and visual impairment were observed in 38 (8%), 96 (20%) and 98 (20%) assessments, with a median time to resolution of 2, 3 and 2 months. Slit lamp examinations by the ophthalmologist (N = 501) revealed a Gr 2 keratopathy in 55 (11%) assessments and Gr 4 keratopathy in 2 ( &lt; 1%) assessments, with a median time to resolution of 4 months. Overall response rate [partial response (PR) or better] was 100.0% [36 pts; stringent complete response: 14% (5 pts); complete response: 19% (7 pts); very good partial response: 47% (17 pts); PR: 19% (7 pts)]. Median time to first response was 1 month. Conclusions: Part 1 of the BelaRd study showed that in TI pts with NDMM, the safety profile of belamaf plus Rd was manageable and a meaningful BCVA decline was noted in a minority ( &lt; 10%) of assessments which resolved quickly (1 month). The combination induced rapid and deep responses, with all pts achieving ≥PR and first response observed at a median of 1 month. Clinical trial information: NCT04808037 .

TREATMENT PATTERNS IN PATIENTS WITH MANTLE CELL LYMPHOMA: UPDATED REPORT OF THE ASIA‐PACIFIC MULTINATIONAL RETROSPECTIVE REGISTRY STUDY

Introduction: We conducted a multinational, multicenter retrospective registry study to better define the treatment patterns and survival outcomes of newly diagnosed patients with mantle cell lymphoma (MCL) in the Asia-Pacific region. Methods: Data were collected from newly diagnosed MCL patients between January 2008 and September 2019 from 27 hospitals in Asian countries, including China, Malaysia, Japan, Singapore, South Korea, Taiwan, and Thailand. The first interim analysis with 191 patients was previously reported. An updated analysis of 289 patients was performed at the data cutoff date of December 19, 2022. Results: The median age was 64 years (range, 26–90), and 213 patients were male (73.7%). The majority of the patients had stage 3 or 4 diseases (n = 249, 86.2%). The most frequently administered 1st line regimen was R-CHOP or R-CHOP-like regimens (n = 146), followed by cytarabine-containing regimens (n = 78) including R-Hyper-CVAD (n = 56), and bendamustine-rituximab (n = 22) (Figure 1A). Higher proportion of elderly patients received R-CHOP or R-CHOP-like regimens, while cytarabine-containing regimens were more frequently administered in young patients (Figure 1B). The overall response rate (ORR) and the complete response (CR) rate among these patients were 94.7% and 59.0%, respectively. The ORR and CR rates for each regimen were as follows; R-CHOP or R-CHOP-like regimens (ORR 97.0%, CR 52.2%), cytarabine-containing regimens (ORR 94.6%, CR 65.3%), and bendamustine-rituximab (ORR 95.2%, CR 76.2%). Median progression-free survival (PFS) was 47.6 months, and median overall survival (OS) was 75.7 months. The median PFS was 41.1 months for R-CHOP or R-CHOP-like regimens, 60.8 months for cytarabine-containing regimens, and 71.0 months for bendamustine-rituximab. Twenty-nine patients received rituximab maintenance treatment, and the survival outcomes regarding maintenance therapy will be updated and presented at the ICML 2023. There were no significant differences in PFS and OS between the ASCT (n = 103) and non-ASCT (n = 35) groups among transplant-eligible patients (n=138), with a 5-year PFS rate of 48.6 versus 32.5% (P = 0.29) and 5-year OS rate of 73.7 versus 73.7% (P= 0.13), respectively. A total of 152 patients were given the 2nd line regimens. The most commonly used regimen was ibrutinib (n = 45), followed by cytarabine-based regimens (n = 38). The median 2nd PFS was 17.3 months. Keyword: Aggressive B-cell non-Hodgkin lymphoma The research was funded by: The work was funded by a research grant from Janssen Pharmaceuticals Ltd. No conflicts of interests pertinent to the abstract.

Impact of minimal residual disease standardised assessment by FDG-PET/CT in transplant-eligible patients with newly diagnosed multiple myeloma enrolled in the imaging sub-study of the FORTE trial.

18F-FDG-PET/CT is the current standard technique to define minimal residual disease (MRD) outside the bone marrow (BM) in multiple myeloma (MM), recently standardised applying the Deauville scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) and defining the complete metabolic response (CMR) as uptake below the liver background (DS<4). In this analysis, we aimed at confirming the role of CMR, and complementarity with BM multiparameter flow cytometry (MFC) at 10-5, in an independent cohort of newly diagnosed transplant-eligible MM patients previously enrolled in the phase II randomised FORTE trial. 109 of the 474 global patients enrolled in the trial between February 23, 2015, and April 5, 2017, who had paired PET/CT (performed at baseline [B] and preceding maintenance therapy [PM]) and MFC evaluation, were included in this analysis. At B, 93% of patients had focal lesions within the bones (FS≥4 in 89%) and 99% increased BM uptake (BMS ≥4 in 61%). At PM, CMR was achieved in 63% of patients, which was a strong predictor for prolonged PFS in univariate analysis at landmark time PM (HR 0.40, P=0.0065) and in Cox multivariate analysis (HR 0.31, P=0.0023). Regarding OS, a trend in favour of CMR was present in univariate (HR 0.44, P=0.094), and Cox multivariate model (HR 0.17, P=0.0037). Patients achieving both PET/CT CMR and MFC negativity at PM showed significantly extended PFS in univariate (HR 0.45, P=0.020) and multivariate analysis (HR 0.41, P=0.015). We herein confirm the applicability and validity of DS criteria to define CMR and its prognostic relevance and complementarity with MFC at the BM level. Amgen, Celgene/Bristol Myers Squibb, Italian Ministry of Health (RC-2022-2773423).

Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials.

There is no standard first-line immunochemotherapy regimen for transplant-ineligible patients with mantle cell lymphoma (MCL) currently, and the efficacy of various treatment remains unclear. We conducted a Bayesian network meta-analysis (NMA) of all eligible randomized controlled trials. Pairwise comparisons and ranking of different first-line treatment options were performed. Nine studies were included in the NMA, involving a total of 2897 MCL patients. The BR-Ibrutinib+R regimen showed the best progression-free survival (PFS), with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69%. The VR-CAP regimen was the most potential intervention to improve overall survival (OS), with a SUCRA of 0.89 and PbBT of 63%. Compared with the R-CHOP regimen, the BR regimen achieved a better PFS (hazard ratio [HR] 0.45 [95% credible interval 0.2-0.96]). The BR-Ibrutinib+R regimen (HR 0.14 [0.02-0.99]), BR+R regimen (HR 0.19 [0.034-0.99]), and BR regimen (HR 0.3 [0.08-1.03]) were superior to CHOP regimen with better PFS. The R-FC regimen (HR 2.27 [1.01-5.21]) or FC regimen (HR 3.17 [1.15-8.71]) was inferior to the VR-CAP regimen with a worse OS. Our study presents the most promising first-line treatment strategy for transplant-ineligible MCL patients in terms of PFS and OS, which provides innovative treatment strategy for MCL treatment.

Real-world analysis of D-RVd v. RVd at induction for newly diagnosed transplant eligible multiple myeloma patients.

e20024 Background: Daratumumab with lenalidomide, bortezomib, and dexamethasone (D-RVd) induction chemotherapy (IC) has recently been shown to improve depth of treatment response for transplant-eligible newly diagnosed multiple myeloma (NDMM) patients (pts) compared to RVd alone. The aim of this real-world data (RWD) retrospective study is to assess the efficacy and depth of response of D-RVd IC compared to RVd in transplant-eligible pts with NDMM. Methods: HealthTree Cure Hub for Multiple Myeloma (PMID: 35271305) an online portal for pts with plasma cell dyscrasias, was used to analyze validated RWD of 59 pts who received D-RVd to 121 pts with similar clinical characteristics but who received RVd at IC. Of the total 180 pts, 84 had completed IC and were at the initiation of maintenance (MT) at the time of this analysis. Patients that progressed prior to reaching MT or whose treatment deviated from the line of therapy (D-RVd/RVd IC, autologous stem cell transplant [ASCT], and MT, with or without consolidation) were also excluded. Response during MT was assessed using IMWG criteria. Results: From the 180 pts reviewed, 98 were excluded, 5 D-RVd and 10 RVD pts progressed before reaching MT, 11 D-RVd and 31 RVd pts deviated from the line of therapy, and 41 pts had not reached the MT phase at the time of the analysis. The remaining 84 pts (18 D-RVd pts and 64 RVd pts) were analyzed. Demographics and clinical characteristics were well-balanced between groups. The median age of both groups was 65 (range, 42-81), and over half were female (51%). The majority of pts (87%) had R-ISS stage I or II, and 45 pts (25%) had high-risk genetics (by mSMART 3.0). The overall response rate (ORR) was significantly higher for the D-RVd group compared to the RVd group at the initiation of MT (100% vs 62%; odds ratio, 22.4; P = 0.03). As assessed prior to the start of MT the depth of response was more favorable with D-RVd, with the odds ratio of achieving a VGPR or better at MT being significantly higher than RVd (89% to 58%; odds ratio (OR), 5.8; P = 0.03), complete response (CR) (78% to 47%; OR, 3.97; P = 0.03), stringent CR (sCR) (22% to 16%; OR, 1.5; P = 0.51), and minimal residual disease (MRD) negativity (17% to 11%; OR, 1.6; P = 0.51). With a median follow-up of 17 months for the D-RVd group (n = 18) and 29 months for the RVd group (n = 64), 0 events of disease progression occurred in the D-RVd group compared to 23 events in the RVd group. Median PFS was not reached in the D-RVd group and a Kaplan-Meier probability indicated a median PFS of 41 months for the RVd group. Conclusions: These data document improved response rate in transplant-eligible NDMM pts who received daratumumab with RVd as an IC therapy. D-RVd also improved PFS with significant differences between the two groups seen at 12 and 18 months. These results add to the accumulating data that the addition of daratumumab with RVd may be the new standard of care for the aforementioned patient population.

Prospective evaluation of minimal residual disease in the phase II FORTE trial: a head-to-head comparison between multiparameter flow cytometry and next-generation sequencing.

Limited data are available on the concordance between multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for minimal residual disease (MRD) detection in a large trial for multiple myeloma (MM) patients. MRD was explored in the FORTE trial for transplant-eligible MM patients randomised to three carfilzomib-based induction-intensification-consolidation treatments and carfilzomib-lenalidomide (KR) vs R maintenance. MRD was assessed by 8-colour 2nd-generation flow cytometry in patients with ≥very good partial response before maintenance. NGS was performed in case of suspected complete response (CR) in a correlative subanalysis. Biological/prognostic concordance between MFC and NGS, conversion to MRD negativity during maintenance, and 1-year/2-year sustained MRD negativity were explored. Between September 28, 2015 and December 22, 2021, 2020 samples were available for MFC and 728 for the simultaneous MFC/NGS correlation in the "suspected CR population". Median follow-up was 62 months. Biological agreement was 87% at the 10-5 and 83% at the 10-6 cut-offs. A remarkable prognostic concordance was observed: hazard ratios in MFC-MRD and NGS-MRD-negative vs -positive patients were 0.29 and 0.27 for progression-free survival (PFS) and 0.35 and 0.31 for overall survival, respectively (p<0.05). During maintenance, 4-year PFS was 91% and 97% in 1-year sustained MFC-MRD-negative and NGS-MRD-negative patients (10-5), respectively, and 99% and 97% in 2-year sustained MFC-MRD-negative and NGS-MRD-negative patients, regardless of treatment received. The conversion rate from pre-maintenance MRD positivity to negativity during maintenance was significantly higher with KR vs R both by MFC (46% vs 30%, p=0.046) and NGS (56% vs 30%, p=0.046). The significant biological/clinical concordance between MFC and NGS at the same sensitivity suggests their possible use in the evaluation of one of the currently strongest predictors of outcome. Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.

EE149 Modelling First-Line Daratumumab Use in Newly-Diagnosed, Transplant-Ineligible Multiple Myeloma in Singapore

The study aims to evaluate the costs and outcomes associated with first-line daratumumab use plus lenalidomide (DRd) for transplant-ineligible multiple myeloma patients, compared to reserving its use for second line following treatment with a bortezomib-based regimen (VRd) from the Singapore health system perspective.

Adjusted indirect treatment comparison of progression-free survival (PFS) associated with DRd and VRd based on MAIA and SWOG S0777 individual patient-level data.

8037 Background: Both daratumumab in combination with lenalidomide and dexamethasone (DRd) and bortezomib in combination with lenalidomide and dexamethasone (VRd) are endorsed by NCCN guidelines as preferred regimens for the treatment of transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). DRd and VRd have each demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) alone in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naive comparisons of efficacy across the 2 trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas S0777 enrolled a mixed transplant-not-intended (TNI) population, which included both TIE patients and patients choosing to defer/refuse frontline stem cell transplantation (median age 63 years). Methods: The present study leveraged individual patient-level data (IPD) from both trials to perform an anchored indirect treatment comparison of DRd vs VRd, adjusting for differences in trial eligibility criteria and baseline patient characteristics. Harmonized inclusion criteria (NDMM, age ≥65 years, ECOG performance status ≤2) were applied to both trial populations. Age ≥65 years served as a proxy for TIE status since S0777 enrolled a mixed TNI population. Propensity score (PS) reweighting was used to balance the 2 trial populations on key baseline prognostic factors including age, sex, ISS stage, ECOG performance status, hemoglobin, eGFR, lactate dehydrogenase (LDH) level, and cytogenetic risk. Missing data were addressed with multiple imputation. After alignment of inclusion criteria and PS reweighting, an anchored indirect comparison was performed wherein within-trial progression-free survival (PFS) hazard ratios (HRs) for DRd vs Rd and VRd vs Rd were estimated and used to make indirect inference about PFS for DRd vs VRd. Results: 727 MAIA participants and 198 S0777 participants were eligible for inclusion. After PS reweighting, the trial populations were balanced on the key baseline prognostic factors identified above (standardized difference &lt; 0.1 for each). The adjusted PFS HRs were 0.53 (95% CI: 0.41–0.68; P&lt; 0.0001) for DRd vs Rd in MAIA and 0.88 (0.63–1.23; P= 0.46) for VRd vs Rd in S0777. In the adjusted Rd-anchored indirect comparison, the PFS HR for DRd vs VRd was 0.60 (0.39–0.90; P= 0.02). Conclusions: In this adjusted indirect treatment comparison based on IPD from the MAIA and S0777 trials, PFS was significantly longer for DRd relative to VRd. In the absence of a head-to-head trial comparing DRd and VRd, the present study may help to inform treatment selection in TIE patients with NDMM.

EFFICACY OF FRONT‐LINE IMMUNOCHEMOTHERAPY FOR TRANSPLANT‐INELIGIBLE MANTLE CELL LYMPHOMA: A NETWORK META‐ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Background: In the past 20 years, there have been significant advances in the prognosis of mantle cell lymphoma (MCL) patients because of the introduction of rituximab. However, there is still no cure, and the relapse is inevitable. The earlier MCL patients progress after the first-line therapy, the worse the prognosis, especially for those who progress within 6 months after first-line therapy. There is no standard first-line immunochemotherapy regimen for transplant-ineligible patients with MCL currently, and the efficacy of various treatment remains unclear. Methods: Network meta-analysis (NMA) can compare the relative treatment effects of multiple interventions by synthesizing evidence from a network of randomized controlled trials (RCTs), which can be very useful for the choice of clinical treatment plans. We conducted a Bayesian NMA of all eligible randomized controlled trials. Pairwise comparisons and ranking of different first-line treatment options were performed. Results: nine studies were included in the NMA, involving a total of 2,897 MCL patients. The BR-Ibrutinib+R regimen showed the best progression-free survival (PFS), with a surface under the cumulative ranking curve (SUCRA) of 0.89 (Figure 1a) and probability of being the best treatment (PbBT) of 69%, followed by the BR+R regimen (SUCRA 0.76, PbBT 11%) and the BVR regimen (SUCRA 0.64, PbBT 13%). The VR-CAP regimen was the most potential intervention to improve overall survival (OS), with a SUCRA of 0.89 (Figure 1b) and PbBT of 63%, followed by the BR regimen (SUCRA 0.74, PbBT 22%) and the R-CHOP regimen (SUCRA 0.65, PbBT 1%). Compared with the R-CHOP regimen, the BR regimen achieved a better PFS (hazard ratio [HR] 0.45 [95% credible interval 0.2–0.96]). The BR-Ibrutinib+R regimen (HR 0.14 [0.02–0.99]), BR+R regimen (HR 0.19 [0.034–0.99]), and BR regimen (HR 0.19 [0.08–1.03]) were superior to CHOP regimen with better PFS. The R-FC regimen (HR 2.27 [1.01–5.21]) or FC regimen (HR 3.17 [1.15–8.71]) was inferior to the VR-CAP regimen with a worse OS. The research was funded by: This work was supported by Achievement Transformation Project (No. CGZH21001), 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21007), Translational Research Grant of NCRCH (No. 2021WWB03), Chengdu Science and Technology Program (No. 2022-YF05-01443-SN, 2022-YF05-01444-SN), Key Research and Development Program of Sichuan Province (No. 2023YFS0031, 2023YFS0306), National Natural Science Foundation of China (No. 82204490), and National Key Research and Development Program of China (No. 2022YFC2502600, 2022YFC2502603). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Chemotherapy, Immunotherapy No conflicts of interests pertinent to the abstract.

HSD56 Provider Perceptions Impacting Treatment Choice in Mantel Cell Lymphoma (MCL): An Analysis of the Shine Trial Evaluating Ibrutinib + Bendamustine and Rituximab (I+BR) Versus Bendamustine and Rituximab (BR) in First-Line (1L)

The SHINE trial (NCT01776840) evaluating I+BR versus BR in 1L for transplant-ineligible patients aged ≥65 years with stage II-IV MCL met its primary endpoint of improved progression-free survival. The discontinuation rates in the I+BR and BR arms were similar (84% and 77% respectively) with more intolerance in the I+BR arm and more progression in the BR arm. Statistically significant clinical trial outcomes are not always clinically meaningful to prescribers, especially in chronic and life-threatening disease states where improved overall survival is not a demonstrated outcome. We conducted qualitative research to understand physicians’ perceptions of SHINE results and impact on future adoption.

Clinical characteristics and prognosis of a Chinese cohort with systemic light chain amyloidosis: a single-center study.

Light chain amyloidosis is a plasma cell dyscrasia characterized by deposition of misfolded amyloid fibrils in tissues, leading to multi-organ dysfunction. We retrospectively analyzed 335 patients (median age, 60years) with systemic light chain amyloidosis in the First Hospital of Peking University from 2011 to 2021. Involved organs were the kidney (92.8%), heart (57.9%), liver (12.8%) and peripheral nervous system (6.3%). Chemotherapy was administered to 55.8% (187/335) of patients, among whom 94.7% received novel agent-based regimens. Hematologic response (≥ very good partial response) was achieved in 63.4% of patients who received chemotherapy. Only 18.2% of patients received autologous hematopoietic stem cell transplant (ASCT). Among transplant-eligible patients, the overall survival of ASCT recipients was better than those who received chemotherapy only. The median overall survival of the patients with light chain amyloidosis was 77.5months. Estimated glomerular filtration rate and Mayo 2012 stage were independent prognostic factors for overall survival in multivariate analysis. Although the younger age and high ratio of renal involvement might contribute to the favorable prognosis of this cohort, the role of novel agents and ASCT is also discernible. This study will provide a comprehensive perspective on progress in treatment of light chain amyloidosis in China.

ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma

Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens—bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04–0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.

Rituximab/bendamustine/cytarabine for transplant-eligible patients with mantle cell lymphoma: A retrospective study.

Mantle cell lymphoma is considered an aggressive B-cell lymphoma. The optimal induction regimen remains controversial as no randomized controlled trial has compared the efficacy of different induction therapies. Herein, we performed a retrospective analysis of the clinical characteristics of 10 patients who received induction treatment consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, bendamustine, and cytarabine (R-BAC) at Toranomon Hospital between November 2016 and February 2022. Although one patient discontinued R-BAC therapy due to a rash, the other nine completed the scheduled chemotherapy. All patients achieved complete response, underwent high-dose chemotherapy and autologous stem cell transplantation, and maintained complete remission with a median follow-up of 15 months. Hematological adverse events (AEs) occurred in all patients; however, none developed documented infection. There were also no fatal non-hematological AEs specific to R-BAC. R-CHOP/R-BAC may be a good induction therapy for transplant-eligible patients with mantle cell lymphoma.

Significance of the pee-value: relevance of 24-hour urine studies for patients with myeloma

International Myeloma Working Group (IMWG) response criteria require refrigerated 24-hour urine specimens for most patients. However, given that serum free light chain testing has been shown to outperform 24-hour urine immunofixation as a prognostic marker, the importance of maintaining urine testing options or requirements within each level of IMWG response criteria has not been investigated. We analyzed responses to induction therapy for all transplant-eligible patients with multiple myeloma at our institution over a 3-year period using traditional versus ‘urine-free’ IMWG response criteria (where references to urine were removed from the descriptions for every depth of response). Of 281 evaluable patients, responses changed for only 4% of patients (95% confidence interval 2–7%) using urine-free criteria. Our results call into question the continued requirement for 24-hour urine measurements as part of IMWG response assessments for all patients. Research into the prognostic performance of urine-free IMWG criteria is ongoing.

Management of Multiple Myeloma: A Review for General Practitioners in Oncology

Multiple myeloma (MM) is a malignant clonal plasma cell disorder in the bone marrow and is the second-most common hematologic malignancy in adults. Although patients with MM have a moderate life expectancy, it remains a heterogeneous disease that often requires multiple lines of chemotherapy for durable control and long-term survival. This review outlines current management strategies for both transplant-eligible and transplant-ineligible patients as well as for relapsed and refractory disease. Advances in drug therapies have widened management options and improved survival. In this paper, we also discuss implications for special populations and survivorship care.

Recent advances in the treatment of multiple myeloma

Background: Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by anemia, renal failure, hypercalcemia, and osteolytic bone lesions. Although it is a complex and challenging disease, recent advances in treatment options have improved outcomes for patients with MM. In this review, we will discuss the recent treatment strategies for MM and introduce emerging agents.Current Concepts: One breakthrough in the field of MM has been the development of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These agents have been shown to markedly improve survival in patients with MM. Furthermore, high-dose chemotherapy with autologous stem cell transplantation remains important in the treatment of transplant-eligible patients. More recently, new immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy or bispecific monoclonal antibodies and agents with new mechanisms of action, have shown promise in the treatment of MM, particularly in patients with relapsed or refractory MM. The recent advancements in MM treatment have greatly improved patient outcomes and offer hope for a cure.Discussion and Conclusion: MM remains an incurable blood cancer owing to repeated relapses. However, the development of CAR T-cell therapies and double-antibody therapies has resulted in remarkable effects in recent clinical trials. Furthermore, combination therapies based on these agents have emerged, and the effectiveness of these agents and combination therapies in the early stages of the disease is being assessed in various clinical trials. Therefore, a cure for MM may soon be possible if the results of these clinical trials are reported and adopted into practice.

Current Main Topics in Multiple Myeloma.

Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease.

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study.

The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone; VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone; D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd. Newly diagnosed MM patients aged ＞18 years who underwent induction therapy followed by autologous stem cell transplantation (ASCT) between November 2020 and December 2021 were identified. Finally, patients with VRd (N=37) and those with D-VTd (N=43) were enrolled. After induction, 10.8% of the VRd group showed stringent complete remission (sCR), 21.6% showed complete response (CR), 35.1% showed very good partial response (VGPR), and 32.4% showed partial response (PR). Of the D-VTd group, 9.3% showed sCR, 34.9% CR, 48.8% VGPR, and 4.2% PR (VGPR or better: 67.6% in VRd vs. 93% in D-VTd, P=0.004). After ASCT, 68.6% of the VRd group showed CR or sCR, while 90.5% of the D-VTd group showed CR or sCR (P=0.016). VRd was associated with an increased incidence of skin rash (P=0.044). Other than rashes, there were no significant differences in terms of adverse events between the two groups. Our study supports the use of a front-line quadruplet induction regimen containing a CD38 monoclonal antibody for transplant-eligible patients with newly diagnosed MM.