Search

Background Multiple myeloma is a highly heterogeneous disease. Super-aged patients with multiple myeloma are a special group. There is a lack of evidence-based medical basis in the treatment decision and general evaluation of them, and there is also some controversy in the assessment of frailty. Objective To explore the clinical features and the influencing factors of survival and prognosis in newly diagnosed super-aged multiple myeloma (MM) patients with the bortezomib based regimen and to evaluate the best assessment model for the general status of patients with MM. Methods The clinical data of newly diagnosed super-aged patients with MM in Beijing Chao-yang Hospital, Capital Medical University from November 2013 to January 2023 were retrospectively analyzed. Survival follow-up was conducted through the medical record system of Beijing Chao-Yang Hospital, Capital Medical University until April 1, 2023, with the end points of this study of overall survival (OS) and progression-free survival (PFS) . The patients were divided into the two-drug treatment group (n=18) and three-drug treatment group (n=11) , and the clinical and genetic characteristics of the two groups were compared. The Geriatric Assessment System (GA) score, UK Myeloma Research Alliance Risk Profie (MRP) score, and Mayo score were used to evaluate the frailty status and treatment efficacy. Survival curves of OS and PFS in MM patients were plotted using the Kaplan-Meier method. Log-rank test was used to compare the survival curves of different influencing factors. Multivariate Cox hazard risk regression analysis was used to explore the influencing factors of OS and PFS in MM patients. Results The median PFS was 8.70 (1.90-43.87) months and the median OS was 17.23 (2.00-72.83) months. A total of 21 (72.41%) patients experienced disease progression (PD) or relapse, and 12 (41.38%) patients died by the final follow-up. The objective remission rate (ORR) for first-line treatment was 82.76% (24/29) , the partial remission (PR) rate was 51.72% (15/29) , the very good partial remission (VGPR) rate was 24.14% (7/29) , and the complete remission (CR) rate was 6.90% (2/29) . There was no significant difference in CR rate, VGPR rate, PR rate and ORR between the two groups of newly diagnosed super-aged MM patients (P>0.05) . Multivariate Cox hazard risk regression analysis showed that MRP debilitation (HR=0.213, 95%CI=0.049-0.924, P=0.039) , elevated serum corrected calcium (HR=0.153, 95%CI=0.041-0.570, P=0.005) and maintenance therapy (HR=4.301, 95%CI=1.219-15.169, P=0.023) were independent influencing factors of PFS in newly diagnosed super-aged MM patients, while maintenance treatment (HR=4.372, 95%CI=1.049-18.221, P=0.043) was an independent influencing factor for OS in newly diagnosed super-aged MM patients. Conclusion There is no significant difference in the efficacy and prognostic impact of two-drug or three-drug Bortezomib based treatment. Serum corrected calcium elevation and maintenance therapy are independent prognostic factors for survival. MRP score can be used to assess the prognosis of newly diagnosed super-aged MM patients.

Background Chimeric antigen receptor (CAR) -T cell immunotherapy has achieved good therapeutic effect in multiple myeloma (MM) , and the most common target is B cell maturation antigen (BCMA) . The disadvantage of single target CAR-T cell immunotherapy is that it can lead to disease resistance and recurrence, which may be related to antigen escape. Therefore, the dual-targeted CAR-T cell therapy for refractory-relapsed multiple myeloma (RRMM) has been improved and developed, but there is still a lack of systematic clinical analysis in this field. Objective A meta-analysis was conducted on the efficacy and safety of dual-targeted CAR-T cell therapy for RRMM patients. Methods PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, and VIP were searched for single-group rate studies on dual-targeted CAR-T cell therapy in patients with RRMM from inception to 2023-02-06. The data were extracted for collection by 2 investigators using a self-designed form and the quality of literature was evaluated using the methodological index for non-randomized studies (MINORS) . The data analysis was conducted using RStudio software. Results A total of 9 clinical studies, involving 200 RRMM patients who had previously received multi-line therapy were included in the study. Dual-targeted CAR-T cell therapy can be mainly divided into four categories based on different targets of BCMA/CD19, BCMA/CD38, BCMA/TACI, and BCMA/CS1, of which the BCMA+CD19 target is more studied. Dual-targeted CAR-T cell therapy also can be divided into four categories of bispecific categories, combined/sequential infusion of two different CAR-T cells, bicistronic or cotransduction according to the different forms of infusion. Meta-analysis showed that the overall response rate (ORR) of dual-targeted CAR-T cells for RRMM was 90.0% (95%CI=0.849-0.943) , and the complete response rate (CRR) was 54.6% (95%CI=0.416-0.673) , the negative rate of minimal residual disease (MRD) was 75.6% (95%CI=0.489-0.952) , the ORR of extramedullary diseases (EMD) was 55.1% (95%CI=0.234-0.851) , the recurrence rate at the last follow-up was 29.7% (95%CI=0.141-0.454) , and the survival rate was 75.6% (95%CI=0.554-0.915) . The incidence of grade 3 to 4 cytokine release syndrome (CRS) was 16.4% (95%CI=0.094-0.245) , and the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 4.0% (95%CI=0-0.120) . Sensitivity analysis suggested stable results. The results of Egger's test indicated a potential bias risk for ORR (P=0.03) and overall response rate of EMD (P=0.02) . Meanwhile, no publication bias was suggested for CRR (P=0.53) , MRD negative rate (P=0.79) , recurrence rate at the last follow-up (P=0.71) , survival rate (P=0.98) , incidence of grade 3-4 CRS (P=0.90) , and incidence of ICANS (P=0.30) . Conclusion Dual-targeted CAR-T cell therapy for RRMM has shown favorable efficacy and safety, and multicenter, large-sample, and longer follow-up studies are needed to further evaluate its efficacy and safety.

Background: Maintenance therapy with proteasome inhibitors (PIs) can improve outcomes of multiple myeloma (MM) patients, however, the neurotoxicity and parenteral route of bortezomib limit its long‐term use. An efficacious, tolerable, and convenient PI option is needed. Methods: In this single‐center, real‐world study, we retrospectively analyzed the outcome and safety profile of ixazomib‐based maintenance therapy in patients who plateaued with the responses of steady disease or better after bortezomib‐based induction therapy in MM patients not undergoing transplantation. Results: Of all the 71 patients, 37 cases (52.1%) were newly diagnosed MM (NDMM) and 34 cases (47.9%) were relapsed and/or refractory MM (RRMM). The overall response rate (ORR) was 81.7%, including 34 patients (47.9%) with a very good response rate or better (≥VGPR) after a median of nine cycles (6–14) of bortezomib‐based induction therapy. Then the ORR was transformed to 74.6% including 39 patients of ≥VGPR (54.9%) after a median of six courses (2–25) of ixazomib‐based maintenance therapy. Of these, 18 patients (25.4%) exhibited responses deepened. With 26.5 months median follow‐up, median progression‐free survival (PFS) was 28.4 and 16.5 months from the start of bortezomib and 16.2 and 10.0 months from the initiation of ixazomib in NDMM and RRMM group, respectively. Moreover, responses deepened during the maintenance phase (hazard ratio: 0.270, p = 0.007), and responses of ≥VGPR during the induction phase (hazard ratio: 0.218, p < 0.001) were confirmed to independently predict longer PFS after multivariate analyses. Severe adverse events (grade 3/4) were relatively rare. Bortezomib‐emergent peripheral neuritis (PN) was significantly relived after the transition to ixazomib (p < 0.001). Conclusion: This real‐world analysis has demonstrated oral ixazomib is a favorable option of long‐term administration for maintenance with efficacy and feasibility and confirmed the association between deepening responses with ixazomib and prolonged PFS. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical efficacies and toxicities of lenalidomide combination chemotherapy in the treatment of relapsing or refractory multiple myeloma (MM) patients., Methods: A total of 14 MM patients were recruited to receive lenalidomide combination chemotherapy in Beijing Chaoyang hospital from June 2013 to October 2014. Lenalidomide 25 mg was taken orally daily or every alternate day for 21 days and resting for 7 days. The regimens were RD (lenalidomide and dexamethasone, n = 6), RCD (lenalidomide, ifosfamide and dexamethasone, n = 4), RDD (lenalidomide, liposomal doxorubicinand dexamethasone, n = 1), PRD (lenalidomide, velcade and dexamethasone, n = 1) and R+DECP (lenalidomide, cisplatin, etoposide, ifosfamide and dexamethasone, n = 2)., Results: Among them, two patients died during the first cycle of lenalidomide. Ten patients finished 2 cycles of treatment and 2 patients attained near complete remission or complete remission (nCR/CR), 6 partial remission (PR) and 2 stable disease (SD) with an overall response rate (ORR) of 8/10. Ten patients finished 3 cycles of treatment and 3 attained CR, 5 PR and 2 SD. Nine patients finished 4 cycles of treatment and 3 attained CR, 5 PR and 1 progressive disease (PD). Six patients finished 5 cycles of treatment and 1 attained CR, 3 PR and 2 PD. Three patients finished 6 cycles of treatment and 1 attained CR, 1 PR and 1 PD. And the most common adverse reactions were fatigue, loss of appetite and hypocytosis. Six patients died., Conclusion: The lenalidomide combination chemotherapy is both efficacious and safe in the treatment of relapsing or refractory MM.

Objective: To explore the clinical effect and toxicity of (cisplatin, etoposide, ifosfamide & dexamethasone) DECP combination chemotherapy in the treatment of relapsing and refractory multiple myeloma (MM) with extramedullary plasmacytomas., Methods: A total of 20 relapsed and refractory MM patients with extramedullary plasmacytomas treated with DECP regimen from May 2005 to May 2013 were analyzed retrospectively. DECP protocols included cisplatin 20 mg/m(2), Day 1-3; etoposide 100 mg/d,Day 1-3; ifosfamide 500 mg·m(-2)·d(-1), Day 1-4; dexamethasone 20 mg/d, Day 1-4. Efficacy was evaluated after 2 therapeutic cycles., Results: After 2 therapeutic cycles, the objective response rate (ORR) was 55% (11/20). After 3 therapeutic cycles, the ORR was 7/12.Seven patients completed 4 cycles with an ORR of 4/7. Two patients had finished 6 cycles and continued to maintain partial remission. The most common adverse events included gastrointestinal reaction and myelosuppression. The median follow-up time was 30 (12-80) months. The median time of overall survival (OS) was 30 (9-121) months. The 1-year OS was 73%, 2-year OS 28% and 3-year OS 21%., Conclusion: The DECP chemotherapy is both effective and safe in the treatment of relapsed and refractory MM patients with extramedullary plasmacytomas.

Objective: To explore the expression of WT1 gene in leukemia patients and its clinical implications., Methods: Expression of WT1 mRNA was detected in two leukemia cell lines (K562 and HL-60), 49 acute leukemia (AL) patients, 33 chronic myeloid leukemia (CML) patients and 25 healthy subjects by reverse trans-criptase-nested polymerase chain reaction (RT-Nested PCR)., Results: WT1 gene was expressed in all subtype of AL including K562 and HL-60 cell lines, 21/29 newly diagnosed and relapsed AL patients, 1/20 complete remission (CR) AL patients, 15/18 CML blastic crisis patients, 1/5 CML patients in accelerated phase, and 1/10 CML patients in chronic phase. WT1 gene was undetectable in 25 healthy subjects. The expression level of WT1 gene was related to the prognosis of AL, patients with relative level >/= 1.0 had lower CR rates and disease-free survival. For CML patients, WT1 gene expression was associated with the clinical phase, it increased with disease progressed., Conclusion: WT1 gene expression is associated with pathogenesis of leukemia. It is a prognostic factor and a marker for the detection of minimal residual disease in AL and may used as an indicator for diagnosing CML blastic crisis.