Clinical Lymphoma, Myeloma & Leukemia最新文献

Background: Chimeric antigen receptor-T (CAR-T) cell therapies are highly effective in treating hematologic malignancies. Cases of second primary malignancies (SPMs) have been reported post-treatment, although risk factors remain unclear. This real-world study evaluated predictors of SPMs among patients treated with CAR-T.

Methods: Patients with multiple myeloma (MM) or lymphoma/leukemia treated with CAR-T were identified from the Komodo Research Database (January 1, 2016-June 30, 2024). Incidences of SPMs and hematologic SPMs were evaluated following CAR-T infusion (index date) and predictors were evaluated 12 months pre-index. LASSO regression was used to identify predictors of SPMs and hematologic SPMs, separately. Multivariate Cox regression was used to assess the magnitude and direction of each predictor.

Results: Among 2,609 patients receiving CAR-T (MM: 683, lymphoma/leukemia: 1,926) and over a median follow-up of 14.5 months, the incidences of SPMs and hematologic SPMs were 11.8% and 5.0%, respectively (0.3% for peripheral T-cell lymphoma). Median time-to-event was approximately 8 months for SPMs and hematologic SPMs. Adjusting for other predictors in the models, there was no association between CAR-T indicated for MM versus lymphoma/leukemia and the risk of SPMs (hazard ratio: 0.85, P = .32). Relative to lymphoma/leukemia, MM was associated with a significantly lower risk of hematologic SPMs (hazard ratio: 0.24, P < .05).

Conclusions: This study found no association between CAR-Ts used in MM versus lymphoma/leukemia and the risk of subsequent SPMs, while a lower risk of hematologic SPMs was observed in patients with MM. T-cell malignancies were infrequent. Ongoing research into potential risk factors of SPMs following CAR-T could help inform individualized management strategies.

Background: Autologous stem cell transplantation (ASCT) remains the standard consolidation therapy for multiple myeloma (MM). Peripheral blood stem cell mobilization, performed using G-CSF alone or in combination with chemotherapy (chemo-mobilization), is a crucial step in this process. Although chemo-mobilization enhances CD34⁺ yields, its effect on disease control and post-transplant outcomes in the era of novel agents remains unclear.

Patients and methods: We retrospectively analyzed 67 MM patients who underwent ASCT at our institution. Thirty-two patients (47.8%) received chemo-mobilization with cyclophosphamide (37.5%) or KD-PACE plus G-CSF (62.5%) and 35 (52.2%) received G-CSF alone. The primary endpoint was overall response rate (ORR) at day 90 post-transplant, while transplant outcomes were analyzed as secondary endpoints. Propensity score-adjusted Cox models were used to assess prognostic factors.

Results: Chemo-mobilization yielded a higher median CD34⁺ collection (7.9 × 10⁶/kg vs. 6.6 × 10⁶/kg; P = .035), fewer apheresis sessions (P = .005), and reduced plerixafor use (P = .005) compared with G-CSF alone. Among chemo-mobilized patients, 89% showed decreased tumor burden and 21% achieved improved response pre-ASCT. ORR at day 90 post-ASCT was comparable between groups (90.6% vs. 94.3%; P = .569). Complete remission (CR+sCR) and MRD negativity were higher in the G-CSF cohort (65.7% vs. 43.8%, P = .008; 90% vs. 60%, P = .007). At 20-month median follow-up, 3-year PFS was 48.4% versus 89.6% (P = .031); OS did not differ significantly (P = .230). Achieving ≥ VGPR pre-ASCT predicted improved PFS (HR 4.04, 95% CI, 1.04-15.71; P = .044).

Conclusion: Chemo-mobilization improves stem cell yield and reduces tumor burden without added toxicity. Achieving ≥ VGPR before ASCT was associated with lower relapse risk and superior PFS.

Patients with follicular lymphoma (FL) often respond to frontline treatment; however, frequently relapse multiple times over many years. Given certain groups of patients are at high-risk of poor outcomes, many studies have elucidated predictors of these high-risk groups, including those refractory to frontline treatment, those who undergo histologic transformation to an aggressive lymphoma, those who experience relapse within 24 months of frontline treatment (POD24), and those who have multiple relapses. Studies evaluating strategies to use risk stratification prospectively have thus far not led to improved outcomes. Further study is required to apply our knowledge of risk stratification in FL to changes in therapeutic decision-making.

The treatment landscape of B-cell acute lymphoblastic leukemia (B-ALL) has been transformed by the incorporation of immunotherapy and potent tyrosine kinase inhibitors (TKIs) into frontline regimens, resulting in meaningful improvements in long-term survival. Such advances have allowed for a reduction in both the intensity and duration of chemotherapy without compromising outcomes, a particularly important goal for older adults, who are less tolerant to intensive chemotherapy and often harbor higher-risk disease features, including TP53 mutations that confer resistance to traditional chemotherapy. Largely chemotherapy-free regimens may alleviate some of the poor outcomes that older patients experience; such regimens are under investigation. While the risk factors that portend inferior outcomes for patients with Philadelphia (Ph)-positive B-ALL are still being defined in the setting of immunotherapy-based regimens and more potent TKIs, it is evident that an elevated baseline white blood cell count is a strong predictor of relapse. The role of chimeric antigen receptor (CAR) T-cell therapy as consolidation for patients with high-risk Ph-positive B-ALL is actively being explored, alongside efforts to identify factors that influence CAR T-cell expansion and persistence as determinants of response durability. Advances in more sensitive assessments of measurable residual disease (MRD) using next generation sequencing (NGS) will help inform which patients may benefit from additional consolidative strategies. Novel agents under development include the subcutaneous (SC) form of blinatumomab, which has demonstrated efficacy even in patients with prior blinatumomab exposure. Altogether, these developments frame the next set of questions in ALL, which will be addressed in this review.