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Background: Multiple myeloma (MM), an incurable disease characterized by frequent relapses and a need for multiple treatments, often progresses to a relapse/refractory status resistant to all available drugs and drug classes. Bispecific antibodies, specifically BCMA T‐cell engagers, have emerged as effective treatments for MM, demonstrating impressive efficacy. However, these treatments can adversely affect the immune system, increasing vulnerability to infections. Methods/Results: This study evaluated the efficacy and safety of BCMA T‐cell engagers in 58 Swedish patients with poor MM prognosis. The patients exhibited a 69% overall response rate, with 69% survival and 60% progression‐free survival at 15 months. Conclusions: Despite the risk of infectious complications, the prognosis of MM patients can be significantly improved with vigilant monitoring and proactive management of infections. This real‐world data highlight the potential of BCMA T‐cell engagers in treating MM, emphasizing the need for careful patient monitoring to mitigate infection risks. [ABSTRACT FROM AUTHOR]

Background: The presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression‐free survival (PFS) and overall survival (OS). Methods: At our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD‐negative (MRD−) patients, after information about the national guidelines, were not advised to follow this regimen. Results: Out of the total 228 patients, 175 received ASCT following first‐line induction (MRD− 92 (53%), MRD+ 83 (47%), at 2 months post‐ASCT), while 53 underwent ASCT after second‐line treatment (MRD− 27 (51%), MRD+ 26 (49%), at the same time point). Comparatively, MRD− patients who did not receive maintenance demonstrated better OS than MRD+ patients who received upfront ASCT and maintenance treatment (96% vs. 86%, p = 0.030, at 3 years). However, nonsignificant difference was found in PFS (76% vs. 62%, at 3 years). Furthermore, second‐line ASCT, MRD− non‐maintained patients exhibited significantly better PFS than MRD+ (71% vs. 27%, p > 0.001, at 3 years). However, OS was better but nonsignificant (96% vs. 76%, at 3 years). Fluorescence in situ hybridization (FISH) analysis was performed on 141 out of the 228 patients. Of these, 85 (60%) patients were deemed standard risk (SR), and 56 (40%) were classified as high risk (HR). In the SR cohort, MRD− patients exhibited better PFS and OS than MRD+ patients (71% vs. 59% and 100% vs. 85%, respectively). In the HR cohort, the MRD− patients showed superior PFS but similar OS compared to MRD+ patients (66% vs. 42% and 81% vs. 80%, respectively). Conclusions: Our results indicate that being MRD− is a more crucial prognostic factor for the 3‐year PFS and OS than the presence of high‐risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second‐line setting, suggesting that these patients may require a more intensive treatment approach. [ABSTRACT FROM AUTHOR]

Objectives: Despite the effectiveness of newer drugs for the treatment of multiple myeloma (MM), the outcomes are further improved by subsequent autologous stem cell transplantation (ASCT). Data on effectiveness in older patients are limited. We compared outcomes in patients aged 65–75 years depending on whether they were treated with ASCT or not and compared those to outcomes in patients <65 years. Methods: This was a retrospective, single‐center study. We compared progression‐free survival (PFS) and overall survival (OS) for all MM patients below and above the age of 65 years treated ± ASCT at the Karolinska University Hospital between 2010 and 2020. PFS and OS were calculated by the Kaplan–Meier method. Variables affecting PFS and OS were evaluated using Cox regression model. Results: Both PFS and OS were improved in the group 65–75 years treated +ASCT compared to those treated pharmacologically (p = 0.008 and p < 0.001, respectively). There were no significant differences between patients <65 years and those 65–75 years treated with ASCT. Conclusion: The findings indicate that even patients >65 years should be evaluated as candidates for ASCT. An individualized approach supported by a frailty/geriatric assessment score could assist clinicians to select the appropriate treatment for each patient. [ABSTRACT FROM AUTHOR]

Introduction: Novel drugs and drug combinations have improved outcomes for multiple myeloma patients. However, subgroups of patients still have a poor progression‐free survival (PFS) and overall survival (OS). In an attempt to identify how the novel drugs affect the outcome in standard‐risk and high‐risk patients, respectively, we have investigated 715 multiple myeloma (MM) patients who have undergone high dose treatment followed by autologous stem cell transplantation at our center during 1995 ‐ 2020. Outcomes during three time periods, 1995‐1999 (period I), 2000‐2009 (period II), and 2010‐2020 (period III), were compared separately for standard‐risk and high‐risk patients. Risk stratification was based on chromosome analysis for periods II and III. Results: The whole cohort of patients showed significantly improved OS with time during the three periods being at a median of 5.8, 7.0, and 10.0 years, respectively. There is also a weak tendency for improved PFS, that is, a median of 2.4, 2.6, and 2.9 years, respectively, during the same periods. However, the separate analysis of standard‐risk and high‐risk patients showed that the overall improvement with time was due to improved standard‐risk patients (median OS 8.4 years for the period I and not reached for period II and III). In contrast, no significant improvement was seen in high‐risk patients. For patients with del17p, PFS was even worse during period III as compared to period II (median 1.6 vs 3.2 years respectively). Conclusion: Our results show that the dramatic improvement in outcome for MM patients during the last 20 years only applies for standard‐risk patients, while high‐risk MM patients still are doing poorly, indicating that the novel drugs developed during this time are preferentially effective in standard‐risk patients. New treatment modalities like CAR‐T cells, CAR‐NK cells, and/or bispecific antibodies should be tried in clinical studies early in the course of the disease, especially in patients with high‐risk cytogenetics. [ABSTRACT FROM AUTHOR]

Objectives: The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32), and its importance as prognostic factor has been controversial. The aim was to analyze its prognostic value. Method: In this retrospective study of 469 newly diagnosed myeloma patients, outcomes in patients with (11;14) and standard risk (t(11;14)SR) or high risk (t(11;14)HR) cytogenetics were compared to outcomes of patients without t(11;14) and SR (non‐t(11;14)SR) or HR (non‐t(11;14)HR), respectively. Results: Overall progression‐free survival (PFS) was shorter in t(11;14)SR than non‐t(11;14)SR (median 28.9 vs 35.3 months); however, the difference was not significant (P = .2). Overall survival (OS) did not differ significantly between the groups. In the subgroup of patients that did not receive high‐dose treatment, PFS was shorter for t(11;14)SR compared to non‐t(11;14)SR, 10.6 vs 24.6 months (P = .01). Although OS were shorter for t(11,14)SR compared to non‐t(11;14)SR (5‐year OS 41.7% vs 63.8%), the difference was not significant (P = .1). In HDT patients, no significant difference was observed for OS or PFS between those with or without t(11;14). Conclusion: This study shows that t(11;14) is associated with poorer outcome in MM, particularly in non‐high‐dose‐treated SR patients. It should be considered an intermediate or high‐risk marker in these patients. [ABSTRACT FROM AUTHOR]

Objectives: At our center, patients with multiple myeloma (MM) were treated upfront with bortezomib, cyclophosphamide, and dexamethasone (VCD) until cyclophosphamide was replaced with lenalidomide in the combination (VRD). These treatments have never been compared head‐to‐head in large real‐life patient material. Method: A retrospective analysis of patients treated with VRD and VCD in the first line, both with and without subsequent high‐dose treatment (HDT) and autologous stem cell transplantation. A total of 681 patients were included, 117 receiving VRD (71 with, 46 without HDT) and 564 receiving VCD (351 with, 213 without HDT). Results: Overall response rate (≥partial response) was higher with VRD compared to VCD in the entire VRD group (98% vs 88%, P < 0.001) and in the non‐HDT group (98% vs 79%, P < 0.001). Progression‐free survival (PFS) at 18 months was longer with VRD compared to VCD in the entire VRD group, the non‐HDT group and the HDT group (88% vs 63%, 82% vs 32% and 91% vs 73%, respectively). Overall survival at 18 months was better for VRD‐treated patients in the entire VRD group (95% vs 89%, P = 0.048). Conclusion: Upfront VRD gives better responses and longer PFS compared to VCD in MM patients with or without subsequent HDT. [ABSTRACT FROM AUTHOR]

Dear Editor, We have with interest read the response by Dr. Caravita di Toritto and Dr. Rago to our recently published article entitled "Conditioning with melphalan (Mel) 200 mg/m SP 2 sp and subsequent autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in elderly multiple myeloma (MM) patients compared to standard of care". 9 Badros A, Barlogie B, Siegel E. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Autologous stem cell transplantation in multiple myeloma patients over 70 years: a GIMEMA Lazio working group experience in a retrospective case-control study. [Extracted from the article]

Solitary plasmacytoma ( SP) and plasma cell leukemia ( PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma ( MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study, we report on incidence and survival in PCL/ SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma ( SBP) ( n=124) and extramedullary plasmacytoma ( EMP) ( n=67) have better overall survival ( OS) than MM ( n=3549). Progression to MM was higher in SBP than in EMP (35% and 7% at 2 years, respectively), but this did not translate into better survival in EMP. In spite of treatment developments, the OS of primary PCL is still dismal (median of 11 months, 0% at 5 years). Hence, there is a great need for diagnostic and treatment guidelines as well as prospective studies addressing the role for alternative treatment options, such as allogeneic stem cell transplantation and monoclonal antibodies in the treatment of PCL. [ABSTRACT FROM AUTHOR]

The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients ( n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population ( n = 9 340 682). Median overall survival for non-high-dose treated patients was 2·8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4·9 years) compared to conventional treatment (2·3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6·9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment. [ABSTRACT FROM AUTHOR]

The combination of melphalan and prednisone ( MP) has been the standard treatment of multiple myeloma ( MM). Since the introduction of novel agents, the clinical outcome in MM has improved. Six randomized prospective studies with thalidomide combined with melphalan and prednisone ( MPT) compared to MP have been performed, most of them showing that MPT gives a better response rate and median overall survival ( OS). Amongst 1843 MM patients admitted to 15 Swedish centres, we selected all patients treated with MP and MPT in first, second, third or fourth line of therapy, in total 888 patients treated with MP and 274 with MPT. Patients were evaluated for response rate, OS and Time to Next Treatment. Multivariate Cox model analysis was made to adjust for different criteria at time for MM-diagnosis. The median OS from beginning of first line of treatment was 2.2/4.2 yrs after MP/ MPT respectively, and in second, third and fourth line of treatment 1.8/2.9, 1.4/1.6 and 1.1/1.9 yrs ( P < 0.0001, 0.003, 0.74 and 0.235). The relative risk for death in the MPT group vs. the MP group was 0.61 (95% CI: 0.45-0.84) in first and 0.55 (0.38-0.83), P < 0.01) in second line. Treatment with MPT gave a significantly better OS rate after both first and second line of therapy when compared with treatment with MP only. [ABSTRACT FROM AUTHOR]