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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., Funding Agencies|Cancerfonden; [4-2528/2019]

Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib-lenalidomide-dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients. The main endpoint of the study was undetectable minimal residual disease (MRD) with sensitivity of <10-5 by flow cytometry at any time, and other endpoints were progression-free survival (PFS) and overall survival (OS). We present the preplanned analysis after the last patient has been two years on maintenance. At any time during protocol treatment, 28% (34/120) had MRD < 10-5 at least once. At two years on maintenance, 66% of the patients in the HR group and 76% in the NHR group were progression-free (p = 0.395) and 36% (43/120) were CR or better, of which 42% (18/43) had undetectable flow MRD <10-5. Altogether 95% of the patients with sustained MRD <10-5, 82% of the patients who turned MRD-positive, and 61% of those with positive MRD had no disease progression at two years on maintenance (p < 0.001). To conclude, prolonged maintenance with all-oral ixazomib plus lenalidomide might improve PFS in HR patients., Funding Agencies|BMS

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 th, Funding Agencies|We would like to extend our gratitude to all patients and their families who participated in this study. Their willingness to contribute has been crucial for the continuation of our research. We would also like to acknowledge the invaluable work of our col

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 2years, 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 11months, 0% at 5years). 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.

Multiple myeloma (MM) is an incurable disease with an increasing number of treatment options. The introduction of what are called novel drugs (bortezomib, lenalidomide and thalidomide) was an important step. These treatments have been well studied in clinical trials that involve selected patient groups and that focus on a specific treatment in a specific line of treatment. However, there is scarce information on the survival as a function of the entire treatment sequence. We wanted to clarify the effect of these treatments in a real-life setting. Furthermore, there are several well-known prognostic factors for MM, but the impact of those factors on survival in the era of novel treatment is not fully understood. In this thesis we aimed to: 1) understand in which order the treatments should be given, 2) define factors affecting prognosis, 3) increase the knowledge of cytogenetic abnormalities and their influence on prognosis and choice of treatment. In Paper I, we retrospectively analysed the outcome in high-dose treated (HDT) patients. The patients were divided according to induction therapy. 142 patients had received conventional chemotherapy with either vincristine, doxorubicin, dexamethasone (VAD) or cyclophosphamide, betamethasone (CyBet) and 94 patients had received bortezomib, cyclophosphamide, betamethasone (VCB). We found that the VCB patients had a quicker and better response than the VAD/CyBet group as well as a longer time to progression. In Paper II, we investigated 1 638 consecutive MM patients and compared their survival with that of a sex- and age-matched normal population. The use of novel agents as upfront treatment in non-HDT patients resulted in a significantly longer overall survival (OS) compared to those who received conventional chemotherapy. The OS was further improved by using novel agents in both first and second line of treatment and for these patients the OS approached the survival in the matched normal population. Paper III focused on MM

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.

Background: Induction therapy for multiple myeloma (MM) and remission status before high-dose treatment (HDT) have been shown to be prognostic factors for survival outcome, although the optimal induction therapy is yet to be defined. Methods: We conducted a retrospective analysis of the impact of induction therapy on survival outcome before and after HDT in MM patients. The study included 236 consecutive patients who underwent HDT. Results: One hundred and forty-two patients (62%) were treated with vincristine, doxorubicin and dexamethasone (VAD) or cyclophosphamide and betamethasone (CyBet) and 94 (38%) were treated with bortezomib, cyclophosphamide and betamethasone (VCB) as induction. Time to first and time to best response was faster in the VCB group than in the VAD/CyBet group, with 42 versus 75 (p < 0.001) and 54 versus 88 days (p < 0.001), respectively. After induction therapy, 49% of the patients in the VCB group and 38% in the VAD/CyBet group achieved a very good partial response or better. Multivariate analysis revealed younger age, lower International Staging System stage and induction treatment with VCB as variables associated with favourable time to progression. Conclusions:Outcome measured as response and time to progression before and after HDT in MM differs depending on type of induction treatment and suggests that VCB is a highly effective induction regimen that confers a post-HDT advantage., De två (2) första författarna delar förstaförfattarskapet.

QC 20130311

QC 20130311

QC 20120312