Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Thiotepa-based autologous stem cell transplantation (ASCT) improves survival in primary central nervous system lymphoma (PCNSL), but > 30% of patients are unable to undergo ASCT following commonly used intensive induction regimens.

Methods: This retrospective population-based study included consecutive patients ≥ 18 years old with PCNSL who were intended for ASCT in Alberta, Canada between 2011 and 2022. A reduced-intensity induction protocol was further abbreviated in 2018 to decrease toxicity and expediate ASCT by incorporating rituximab, procarbazine, and only 2 doses of high-dose methotrexate and 1 cycle of high-dose cytarabine before consolidation with thiotepa-busulfan conditioning. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method.

Results: Among 71 patients with median age 58 years (range 26-72), ASCT was completed in 56 (79%), with the transplantation rate among patients > 60 years old increasing by 30% following the abbreviation of induction therapy. With median follow-up time 3.9 years, 4-year PFS and OS were 69% (95% CI 56%-79%) and 80% (95% CI 67%-88%) for all patients and 75% (95% CI 57%-86%) and 85% (95% CI 68%-93%) for ASCT recipients, respectively. There was 1 death due to treatment-related mortality during induction and none after ASCT, including among 17 transplanted patients > 60 years old.

Conclusion: An abbreviated induction regimen followed by thiotepa-busulfan-based ASCT achieves high transplantation rates with low risks of relapse and treatment-related mortality, thereby providing an effective treatment strategy for PCNSL.

Multiple myeloma treatment has evolved rapidly with the development of novel targeted therapies. The paper outlines multiple myeloma epidemiology, current treatments, and recent advances, highlighting the role of bispecific antibodies. Brazilian authorities have approved 3 bispecific antibodies (teclistamab, elranatamab, and talquetamab) for relapsed/refractory multiple myeloma patients who have received at least three prior therapies. These therapies have shown promising efficacy in clinical trials, with 61%-74% overall response rates. However, access to these treatments varies significantly between Brazil's private and public healthcare systems. A panel of 6 Brazilian experts in multiple myeloma and bispecific antibody therapy convened for a three-day virtual conference organized and moderated by Americas Health Foundation. They addressed key questions regarding bispecific antibody therapy in multiple myeloma and developed consensus recommendations. While bispecific antibodies offer new hope for multiple myeloma patients, challenges remain in ensuring equitable access to these therapies. The paper discusses the sequencing of bispecific antibodies with other treatments, the management of adverse events, and the need for real-world data. It also highlights the disparities in multiple myeloma treatment between Brazil's public and private healthcare systems, emphasizing the need for targeted efforts to bridge this gap and improve outcomes for all multiple myeloma patients.

Multiple myeloma (MM) diagnosis requires ≥10% plasma cell (PC) infiltration in the bone marrow (BM), detected by bone marrow aspiration (BMA) or biopsy (BMB). We evaluated the concordance of these 2 techniques in 189 patients. In 43 cases (23%), the techniques were discordant, 10 due to poor sample quality. In the remaining 33 patients, BMB diagnosed MM, while BMA detected < 10% PC, being symptomatic in 16 patients and smouldering (SMM) in 17. Without an initial BMB, 11% would have been misdiagnosed; and 12% of symptomatic patients would require a second BMA or BMB for strict diagnosis according to current criteria.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials and methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

Results: This analysis included: PREAMBLE n = 215; Connect MM n = 232; Flatiron Health n = 845. Median age at index was 69.0 years, median 3 prior lines of therapy; > 50% male. The most common index regimens accounted < 15% of treatments (most common PREAMBLE, Connect MM: carfilzomib±dexamethasone; Flatiron Health: pomalidomide+daratumumab+dexamethasone); most patients received classes that they had previously; ≥ 93% were triple-class exposed (immunomodulatory drug, proteasome inhibitor, anti-CD38 mAb). In PREAMBLE, Connect MM and Flatiron Health, respectively: 80.9%, 68.1% and 77.2% were lenalidomide- and anti-CD38 mAb-refractory; 69.3%, 67.2% and 71.1% were triple-class refractory (TCR); median PFS: 5.2 (95% CI 3.7-6.7), 4.4 (3.5-5.6) and 5.3 months (4.8-6.0); median OS: 19.3 (15.8-26.1), 14.2 (11.0-16.9) and 23.1 months (19.0-28.6). PFS and OS were shorter in lenalidomide- and anti-CD38 mAb-refractory patients versus those who were not refractory to both. A similar pattern was observed for TCR patients versus non-TCR patients.

Conclusion: There is no uniform standard of care for patients with RRMM with prior exposure to lenalidomide and anti-CD38 mAbs. Survival outcomes are poor, with a need for effective treatments for these patients.

Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant condition of multiple myeloma (MM). Evidence suggested old age, black race, male gender, and obesity as risk factors for MGUS development; however, whether they are associated with an increased risk of progression to MM among patients with MGUS is unclear. A systematic search of PUBMED and EMBASE for cohort studies investigating the association between age/race/gender/obesity and progression to MM. We used the Newcastle-Ottawa Scale (NOS) to assess the methodologic quality of the included studies. Summary risk ratios were calculated using random-effects models. We identified 24 publications, of which 17 articles were included in the main analyses. Overall, the quality of the studies was fair (mean NOS = 5.5). Our meta-analyses showed that old age was positively associated with the risk of the MGUS-MM progression (risk ratio: 2.38; 95% confidence interval [CI] 1.59-3.57), while race was not statistically significantly associated with the risk (blacks vs whites: 1.09; 95% CI: 0.77-1.54). Males had a lower risk of MGUS-MM progression, compared to females (risk ratio: 0.70; 95% CI 0.50-1.0; P-value = .048). High body mass index was significantly associated with an increased risk of MGUS-MM progression (risk ratio: 1.32; 95% CI 1.12-1.57). Based on extant research, old age, female sex, and obesity may be implicated in MGUS-MM progression. However, several studies which found an insignificant association between age/gender and progression did not report the risk estimates. Publication bias exists and our risk estimates may be overestimated. More studies are warranted to confirm our findings.

BCR::ABL1-negative myelo-proliferative neoplasms (MPNs) are characterized by mutations in JAK2, CALR, or MPL. Usually these mutations are co-exclusive of each other and of BCR::ABL1. We reviewed clonal interactions in 177 subjects with mutations in JAK2, CALR, or MPL and BCR::ABL1 including JAK2/BCR::ABL1 (N = 142), CALR/BCR::ABL1 (N = 31), MPL/BCR::ABL1 (N = 3). Co-mutations can arise in the same clone or in different sub-clones. In this review we used clonality data, mutation sequencing and therapy response evaluation to address this question. We found that in subjects with JAK2/BCR::ABL1 co-mutations there is a complex, branched clonal evolution. In contrast, in subjects with CALR/BCR::ABL1, co-mutations are in different sub-clones. There are too few data in subjects with MPL/BCR::ABL1 to critically analyze. However, indirect methods for assessing clonality limit our conclusions. Understanding clonal architecture of MPNs with co-mutations is needed to understand the underlying biology and give appropriate therapy.

Background: Invasive fungal disease (IFD) poses significant challenges for critically ill patients with hematological malignancies (HMs). However, there is limited research on the clinical characteristics, risk factors, and outcomes of IFD within this population.

Method: A retrospective study was conducted at a tertiary center in China. The study focused on patients with HMs admitted to the intensive care unit (ICU) between 2014 and 2022.

Results: A total of 239 patients were enrolled, among whom 105 (43.9%) were diagnosed with IFD. Further classification revealed that 64.8%, 31.4%, and 3.8% were classified as possible, probable, and proven IFD, respectively. Patients with IFD had significantly prolonged ICU stays compared to those without IFD (median: 4.9 vs. 2.9 days, P < .001). Notably, there was no statistically significant difference in 28-day mortality between the patients with and without IFD (44.8% vs. 54.5%, P = .907). Hypertension, mechanical ventilation (MV) duration exceeding 48 hours, and an extended interval between deterioration and ICU admission emerged as independent risk factors for IFD.

Conclusion: IFD is a common complication in critically ill patients with HM and is associated with prolonged length of ICU stay. Additionally, hypertension, prolonged MV duration and delayed ICU transfer are independent risk factors of IFD in these patients.

In the past decade, the treatment paradigm for chronic lymphocytic leukemia (CLL) has markedly shifted from traditional chemoimmunotherapy towards targeted therapies.¹ A fixed-duration, targeted regimen with venetoclax, a potent oral BCL-2 inhibitor, combined with obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody (Ven-Obi), has become the standard to beat for time-limited therapy in CLL. Ven-Obi allows for the rapid induction of remissions with high rates of undetectable minimal residual disease (uMRD) in patients across different treatment settings. This strategy enables the discontinuation of therapy while maintaining treatment-free remissions for several years in many patients. With up to 6-year data now available from the pivotal phase 3 trial of this combination in CLL, this review aims to examine the evolving role of this strategy in CLL management, including updated data for safety and efficacy in randomized trials in both the frontline and relapsed/refractory (R/R) settings. We also explore real-world data for this combination, and review related issues, such as MRD monitoring, the potential for venetoclax retreatment or consolidative strategies and evaluate ongoing trials comparing this regimen as a standard of care control arm versus novel (including all-oral) therapeutic combinations.

Introduction: Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic.

Patients and methods: We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas. A total of 24 patients were enrolled with median age 70; 6 patients had diffuse large B-cell lymphoma (DLBCL) and 18 patients had peripheral T-cell lymphomas (PTCL-NOS: 10; angioimmunoblastic T-cell lymphoma [AITL]: 7; ALK-negative anaplastic large cell lymphoma: 1). Patients had received a median of 2 prior lines of therapy and 10 patients were refractory to last line of therapy.

Results: Using a standard 3 + 3 dose escalation design, the maximum tolerated dose of romidepsin was determined to be 10 mg/m² in combination with GemOxD. There were no unexpected toxicities. The most common grade ≥ 3 treatment-emergent adverse events were thrombocytopenia (79%) and lymphopenia (46%). The overall response rate for Romi-GemOxD was 52% (12/23) with complete response (CR) rate of 43% (10/23). All 6 patients with AITL evaluable for efficacy achieved CR. Durable responses were seen in patients with AITL, PTCL-NOS and DLBCL. Without additional therapy, 4 patients remained in remission for more than 2 years, with 3 patients progressing at 46.5, 30.8, and 32.6 months and 1 remission ongoing at 83 months. A total of 4 patients proceeded to consolidative stem cell transplant following induction.

Conclusion: Romi-GemOxD represents a well-tolerated, time-limited, effective option for patients, particularly for those with AITL in which durable responses were seen. NCT02181218.