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Introduction: High-dose therapy with melphalan followed by autologous stem cell transplant in the upfront setting (upfront ASCT) has significantly improved clinical outcomes of myeloma patients and become the standard of care for the past 30 years. However, with the advent of modern induction therapy, the role of upfront ASCT approach has been called into question. Several prospective studies have examined whether continuing with triplet therapy as consolidation with optional ASCT at relapse (triplet-alone) could result in comparable outcomes. Methods: This was a systematic review and meta-analysis of randomized controlled trials comparing upfront ASCT versus triplet-alone approach among myeloma patients treated with triplet therapy, which included two novel agents and a corticosteroid, as induction. Cochrane Library, PubMed and conference proceedings were searched. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), safety, and second primary malignancies (SPM). Subgroup analysis was conducted for high-risk cytogenetics. Results: Our search yielded three trials, conducted between 2010–2018, including 1,737 patients. Two trials evaluated bortezomib plus lenalidomide (VRd) induction and the third study tested carfilzomib plus lenalidomide (KRd) induction. Maintenance was given in all trials to both arms. There was no difference in OS between the arms; the pooled OS in all patients and those with high-risk cytogenetics was hazard ratio (HR) 1.03 (95% CI, 0.85–1.26; I2 = 0%; 1,737 patients, 3 trials) and 0.85 (95% CI, 0.59–1.23; I2 = 0%; 222 patients, 2 trials), respectively. The pooled PFS for upfront ASCT versus triplet-alone was significantly improved in all the patients and in the high-risk cytogenetics subgroup, HR 0.67 (95% CI 0.59–0.76; I2 = 0%; 1,737 patients, 3 trials) and HR 0.59 (95% CI: 0.44–0.7; I2 = 0%; 306 patients, 3 trials), respectively. The risk of any grade 3–4 adverse events was higher in the upfront ASCT arm versus triplet-alone approach (relative risk = 1.17 [95% CI, 1.12–1.23; 1,737 patients]). The risk of secondary malignancies was reported in all three trials and was comparable between both arms. Two trials reported on secondary myeloid neoplasms, which were significantly higher among upfront ASCT arm versus triplet-alone approach, OR 9.7 (1.8–52.25, I2 = 0%, 1,422 patients). Conclusion: Although upfront ASCT approach, in the era of triplet therapy, resulted in a significantly longer PFS among all patients, this did not translate into a survival benefit, regardless of cytogenetic risk. Upfront ASCT was associated with an increased rate of secondary myeloid neoplasms. In the current plethora of innovative therapies, the role of upfront ASCT is debatable. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare disease with an incidence of 0.4/per 100,000 person‐years. As there is a limited number of prospective randomized trials in PCNSL, large retrospective studies on this rare disease may yield information that might prove useful for the future design of randomized clinical trials. We retrospectively analyzed the data of 222 newly diagnosed PCNSL patients treated in five referral centers in Israel between 2001 and 2020. During this period, combination therapy became the treatment of choice, rituximab has been added to the induction therapy, and consolidation with irradiation was largely laid off and was mostly replaced by high‐dose chemotherapy with or without autologous stem cell transplantation (HDC‐ASCT). Patients older than 60 comprised 67.5% of the study population. First‐line treatment included high‐dose methotrexate (HD‐MTX) in 94% of patients with a median MTX dose of 3.5 g/m2 (range 1.14–6 g/m2) and a median cycle number of 5 (range 1–16). Rituximab was given to 136 patients (61%) and consolidation treatment to 124 patients (58%). Patients treated after 2012 received significantly more treatment with HD‐MTX and rituximab, more consolidation treatments, and autologous stem cell transplantation. The overall response rate was 85% and the complete response (CR)/unconfirmed CR rate was 62.1%. After a median follow‐up of 24 months, the median progression‐free survival (PFS) and overall survival (OS) were 21.9 and 43.5 months respectively with a significant improvement since 2012 (PFS: 12.5 vs. 34.2 p = 0.006 and OS: 19.9 vs. 77.3 p = 0.0003). A multivariate analysis found that the most important factors related to OS were obtaining a CR followed by rituximab treatment and Eastern Cooperative Oncology Group performance status. The observed improvement in outcomes may be due to multiple components such as an intention to treat all patients regardless of age with HD‐MTX‐based combination chemotherapy, treatment in dedicated centers, and more aggressive consolidation with the introduction of HDC‐ASCT. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the role of additional chemotherapy before autologous hematopoietic cell transplantation (HCT) in patients with relapse/refractory diffuse large B‐cell lymphoma (DLBCL) who achieve partial remission following first salvage therapy. Methods: We conducted a multicenter retrospective study of all adult patients with DLBCL who underwent HCT between 2008 and 2020 and achieved partial response (PR) after the first salvage and were either referred directly to HCT (n = 47) or received additional salvage therapy before HCT (n = 22). Results: Post‐HCT CR rate and progression‐free survival were comparable between the two groups (66% vs. 68%, p =.86 and median not reached vs. 10.2 months [95% confidence interval, CI 7.1–12.3], p =.27, respectively). Median overall survival (OS) and estimated 3‐year OS favored patients who were directly referred to HCT (105.8 [95% CI 63–148] months vs. 14.5 [95% CI 0–44] months, p =.035, and 65% [95% CI 51%–75%] vs. 40% [95% CI 21%–53%], p =.035, respectively). In Cox regression model, while International Prognostic Index and primary refractory versus relapse disease did not impact OS, allocation to a second salvage regimen and older age were both associated with inferior survival (hazard ratio [HR] = 2.57 95% CI 1.1–5.8, p =.023 and HR = 1.04 95% CI 0.99–1.2, p =.064, respectively). Conclusions: Referring patients with chemotherapy‐sensitive disease in PR directly to HCT is associated with better OS compared to those receiving additional lines of treatment. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) involvement is rare in primary mediastinal large B‐cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system ‐ international prognostic index (CNS‐IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55‐month median follow‐up only 8 patients experienced CNS relapse as first event, always isolated. The 2‐year cumulative incidence of CNS relapse (CI‐CNSR) was 1.47% and remained unchanged thereafter. The CI‐CNSR was not affected by the chemotherapy regimen (R‐CHOP or R‐da‐EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2‐year CI‐CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS‐IPI was also predictive (2‐year CI‐CNSR in high‐risk vs. intermediate/low‐risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement. [ABSTRACT FROM AUTHOR]