Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Chimeric antigen receptor T-cell (CAR-T) therapies are available for patients with Non-Hodgkin Lymphoma (NHL); however, their use has been limited in accessibility due to nondisease factors.

Patients & methods: We conducted a retrospective study evaluating the influence of sociodemographic factors on access and outcomes after CAR-T therapy for adult patients with B-cell NHL in our institution treated between 2016 and 2023.

Results: Among 154 patients treated with CAR-T, 43% were older than 65 years, 68% male, and 14% non-White (including Hispanic). Of those under 65, 66% had private insurance, while 82% over 65 had Medicare. Most patients (85%) were from in-state, 29% from areas below the national poverty level and 18% from nonmetropolitan areas. Distance to the treatment center was greater than 30, 60 or 120 miles for 52%, 40% and 29% of patients, respectively. No significant differences were found in the use of commercial versus investigational products among racial/ethnic minorities or those living >60 miles from the center. However, patients from nonmetropolitan areas and those below the national poverty level were less likely to receive commercial products. With a median follow-up of 11 months, the 1-year overall survival (OS) was 63.2% (95^th CI 59.9%-66.8%). Poverty was associated with lower 1-year OS (HR 0.4, 95^th CI 0.17-0.90, P = .031).

Conclusion: Our study shows that CAR-T therapy can be delivered across sociodemographic barriers and underscores the importance of considering social determinants of health to optimize access for all patients.

Background: Tyrosine kinase inhibitors (TKIs) are the mainstay treatment for chronic myeloid leukemia in chronic phase (CML-CP). Asciminib, an ABL/BCR::ABL1 inhibitor which binds to the myristoyl pocket, was recently approved in the US for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation. This study described treatment patterns and real-world clinical outcomes among patients with CML-CP treated with asciminib in US clinical practice.

Methods: Electronic health record data from adult patients with CML-CP who initiated asciminib after ≥2 prior TKIs, without the T315I mutation, were obtained from the Flatiron Health database. Time-to-treatment discontinuation and molecular response (MR; time-to-BCR::ABL ≤0.1% and time-to-BCR::ABL1 ≤1%, separately) were evaluated from asciminib initiation (index date) using Kaplan-Meier analyses.

Results: Overall, 97 patients initiated asciminib (median age: 63 years, 50.5% female, 64.9% White) after either 2 (47.4%) or 3 (24.7%), or ≥4 (27.8%) prior TKIs. In total, 85.7% and 78.1% of patients remained on asciminib by 12- and 24-weeks postindex, respectively. Among patients with ≥1 MR assessment postindex, 31.3% (95% confidence interval [CI]: 21.6%, 43.9%) and 49.7% (95% CI: 38.1%, 62.6%) achieved or maintained BCR::ABL1 ≤0.1%, while 51.3% (95% CI: 40.1%, 63.6%) and 64.2% (95% CI: 52.6%, 75.6%) achieved or maintained BCR::ABL1 ≤1%, by 12- and 24-weeks, respectively.

Conclusions: Results of this real-world study describing clinical outcomes among patients with CML-CP treated with asciminib after ≥2 prior TKIs in the US demonstrated that asciminib was well-tolerated and effective. These findings were consistent with results from the ASCEMBL trial.

Multiple myeloma is a challenging hematological malignancy, with ongoing efforts toward finding a cure. Dr. Raymond Alexanian has been instrumental in advancing the understanding and treatment of multiple myeloma through his pioneering research. Trained at Dartmouth College and Harvard Medical School, Dr. Alexanian MD Anderson Cancer Center career spanned nearly 5 decades. He developed the highly effective MP (melphalan-prednisone) regimen, which became a standard treatment for years. Dr. Alexanian's exploration of steroids, particularly high-dose dexamethasone, and the collaboration with Dr. Bart Barlogie led to the development of the VAD (vincristine, doxorubicin, and dexamethasone) regimen, significantly improving outcomes for refractory cases. He also contributed to the establishment of high-dose melphalan with autologous stem cell transplantation. Dr. Alexanian's work identified critical prognostic factors and contributed understanding indolent and localized myeloma. His efforts in evaluating new agents, including thalidomide and bortezomib, further enhanced treatment options. Beyond research, his compassionate patient care and advocacy have had a profound impact. Dr. Alexanian's legacy continues to inspire advancements in multiple myeloma treatment, with his innovative approaches reshaping the field and fostering the pursuit of a cure.

Introduction: High risk myeloma is heterogeneous with significant variation in risk stratifications. Real world outcomes differ from controlled clinical trials and affected by socioeconomical determinants.

Material and methods: This retrospective study was performed in a North Indian teriarty care cancer hospital. Out of 384,76(19.7%) high risk myeloma patients (median age 58 years) were analyzed.

Result and conclusion: Most common HRCA was 1 q gain 36(47.4%) followed by del17p 32(42.1%). 61/76(80.2%) received bortezomib based triplets and 15(19.74%) daratumumab based quadruplets induction, 31(40.79%) received ASCT. Median duration of follow up was 19.5 months. The 2 year OS and PFS was 73.8%, 52.6% respectively. Estimated 3 year OS was 74.7% in ASCT cohort versus 52.9% (P = .0067) without. Estimated 3-year PFS in the ASCT cohort was 72.1% versus 30.3% (P = .0026) without. Estimated 3-year OS for single hit and multi hit ultra HRMM was 67.7% and 61.9% (P = .642) whereas PFS was 58.2% and 35.2% (P = .486) respectively. In multivariate analysis ASCT correlated with better OS (HR 0.3, P = .041) and PFS (HR 0.35, P = .012). Absence of baseline renal impairment correlated with better OS (HR 4.12, P = .004) only. Early aggressive therapy with prompt ASCT translates to a better survival in high risk myeloma. Emphasis on real world clinical outcome is the need of the hour for addressing practical issues and improving global myeloma outcome.

Myelofibrosis (MF) is a rare hematologic malignancy that is characterized by dysregulation of the JAK-STAT pathway resulting in fibrosis of the bone marrow, splenomegaly, and abnormalities in peripheral blood counts including anemia, leukocytosis, and thrombocytopenia. This disease has 2 phenotypic extremes - myeloproliferative and cytopenic. Cytopenic myelofibrosis presents with pronounced cytopenia and a different landscape of genetic mutations which results in worse clinical outcomes and a poor prognosis. Patients with cytopenic MF are at high risk of developing various complications like bleeding, infections, and transfusion dependency. Historically, the only Federal Drug Administration (FDA) approved therapy was ruxolitinib, a JAK1/2 inhibitor, which improved constitutional symptoms and splenomegaly, however, exacerbated anemia and thrombocytopenia.^1,2 There were very few options for patients with anemia and thrombocytopenia, and supportive treatments for these problems lack efficacy. Fortunately, there are newer treatment options which may allow for treatment of the symptoms and splenomegaly in the setting of cytopenias and even improve cytopenias. This up-to-date review not only highlights the prevalent options in therapeutic marketplace, but also sheds light on the significant unmet need of addressing anemia and thrombocytopenia in cytopenic MF.

Hematopoietic cell transplantation requires higher doses of chemotherapy, and practices of adjusting the weight because of concerns of organ toxicity are common. This retrospective analysis of 239 adult recipients of autologous hematopoietic cell transplantation for lymphoma assessed the effect of obesity on transplantation outcomes.

Background: Prior data evaluating the impact of obesity in autologous hematopoietic cell transplantation (AHCT) for lymphomas have provided differing results when assessing overall (OS) and progression-free survival (PFS). Impact on survival outcomes have been described, but direct comparison of discrete toxicities is lacking.

Patients and methods: We retrospectively compared outcomes with patients divided between 3 groups: nonobese patients (n = 129), obese patients dosed on adjusted body weight (AdjBW) (n = 32), and obese patients dosed on total body weight (TBW) (n = 78).

Results: In multivariate analysis of OS with the nonobese group as the comparator, outcomes trended worse in obese patients dosed on AdjBW (HR 1.22, 95% CI 0.52-2.85) but were improved in obese patients dosed on TBW (HR 0.19, 95% CI 0.04-0.85, P = .012). PFS of obese patients dosed on AdjBW vs. the nonobese group was comparable (HR 1.19, 95% CI 0.63-2.24), but improved in obese patients dosed on TBW (HR 0.45, 95% CI 0.23-0.89, P = .021). Notably, no differences were noted between groups in gastrointestinal, infectious, renal, or hepatic toxicities.

Conclusion: In summary, our data suggest that recipients of AHCT for lymphoma should be dosed on TBW to maximize curative outcomes with no apparent increase in toxicities.

Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by myeloproliferation, bone marrow fibrosis, splenomegaly, and constitutional symptoms related to pro-inflammatory cytokine signaling. Biologically, MF is characterized by constitutive activation of JAK-STAT signaling; accordingly, JAK inhibitors have been rationally developed to treat MF. Following the initial approval of ruxolitinib in 2011, three additional agents have been approved: fedratinib, pacritinib, and momelotinib. As these therapies are noncurative, allogeneic stem cell transplantation remains a key treatment modality and patients with MF who are deemed candidates should be referred to a transplant center. This potentially curative but toxic approach is typically reserved for patients with higher-risk disease, and JAK inhibitors are recommended in the pretransplant setting. JAK inhibitors have proven effective at managing splenomegaly and constitutional symptoms and should be started early in the disease course in patients presenting with these clinical manifestations; asymptomatic patients may initially be followed with close surveillance. Drug-related myelosuppression has been a challenge with initial JAK inhibitors, particularly in patients presenting with a cytopenic phenotype. However, newer agents, namely pacritinib and momelotinib, have proven more effective in this setting and are approved for patients with significant thrombocytopenia and anemia, respectively. Resistance or disease progression is clinically challenging and may be defined by several possible events, such as increasing splenomegaly or progression to accelerated or blast phase disease. However, with multiple JAK inhibitors now approved, sequencing of these agents appears poised to improve outcomes. Additionally, novel JAK inhibitors and JAK inhibitor-based combinations are in clinical development.

Background: T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin).

Patients and methods: We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

Results: Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias.

Conclusions: Overall, EPOCH was well tolerated with high response rates in first line and R/R setting.