scholarly journals Survival of Patients with Multiple Myeloma That Is Refractory to Both Bortezomib and Lenalidomide: A Retrospective Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2020-2020
Author(s):  
Kanji Miyazaki ◽  
Kenshi Suzuki
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Study ◽  
Autologous Transplantation ◽  
Survival Rates ◽  
Allogeneic Transplantation ◽  
New Drugs ◽  
Rank Test ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Better Than

Abstract Introduction: Patients with multiple myeloma that is refractory to both bortezomib and lenalidomide show poor survival. This resistant myeloma is called double-refractory multiple myeloma. Several new drugs, such as pomalidomide, panobinostat, carfilzomib, ixazomib, elotuzumab, and daratumumab, have become available in recent years. These new drugs could prolong the survival of patients with double-refractory multiple myeloma in prospective clinical trials. The present study aimed to evaluate the survival of such patients and assess the effectiveness of the new drugs, autologous transplantation, and allogeneic transplantation in real clinical settings. Methods: This retrospective study reviewed the medical records of patients with multiple myeloma who received treatment between February 2002 and January 2018 at our institution. Patients with myeloma refractory to both bortezomib and lenalidomide were selected. Those with coexisting amyloidosis were excluded. The primary outcome was overall survival (OS). Survival analyses were performed using the Kaplan-Meier method, and survival rates were compared using the log-rank test. Results: The study included 103 patients. New drugs were used in 71 (68.9%) patients, and their OS was significantly better than that of the remaining 32 (31.1%) patients who did not receive those agents (median OS, not reached versus 5 months, p < 0.001) (Figure 1). Total 20 patients underwent autologous transplantation. Their OS was similar to that of those who did not undergo autologous transplantation (median OS, 21 months versus 17 months, p = 0.503). Total 10 patients underwent allogeneic transplantation. Their OS was similar to that of those who did not undergo allogeneic transplantation (median OS, 24 months versus 18 months, p = 0.517). In the 71 patients who were treated using new drugs, pomalidomide and panobinostat-based therapies were not associated with better survival, whereas carfilzomib, ixazomib, elotuzumab, and daratumumab-based therapies were associated with significantly better OS. Carfilzomib was administered to 45.1% (32/71) of patients, and their OS was significantly better than that of the remaining 54.9% (31/71) patients (median OS, not reached versus 19 months, p = 0.032). Although carfilzomib, lenalidomide, and dexamethasone (KRd) therapy was not associated with better OS among the 71 patients, carfilzomib and dexamethasone (Kd) therapy was associated with better OS (median OS, not reached versus 21 months, p = 0.040). Ixazomib was administered to 14.1% (10/71) of patients, and their OS was 100%, which was significantly better than that of the remaining 85.9% (61/71) of patients (median OS, 20 months, p = 0.037). Elotuzumab was administered in 15.5% (11/71) of patients, and their OS was also 100% and was significantly better than that in the remaining 84.5% (60/71) of patients (median OS, 20 months, p = 0.011). Daratumumab was administered in 25.4% (18/53) of patients, and their OS was significantly better than that of the remaining 74.6% of patients (median OS, not reached versus 20 months, p = 0.025). The OS of patients administered only 1 new drug was worse than that of patients administered 2 new drugs (median OS, 17 months versus not reached, p = 0.003). However, the OS of patients administered 2 new drugs was comparable with that of patients administered 3 or more new drugs (p = 0.477) (Figure 2). Conclusions: New drugs, particularly carfilzomib, ixazomib, elotuzumab, and daratumumab, are associated with improved survival in patients with multiple myeloma refractory to both bortezomib and lenalidomide. Autologous and allogeneic transplantation are not associated with improved survival. Figure 1. Figure 1. Disclosures Suzuki: SRL.Inc: Employment; Sanofi Aventis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Ono: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.

Non-Myeloablative Allogeneic Transplantation in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2759-2759
Author(s):  
Sabine Gerull ◽  
Ute Hegenbart ◽  
Martin Goerner ◽  
Axel Benner ◽  
Thomas Moehler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Number Of Cycles

Abstract Patients with recurrent and refractory multiple myeloma have a very limited survival expectance. Allogeneic transplantation might offer an option for cure in myeloma and the recent development of non-myeloablative conditioning regimens has reduced transplant related morbidity and mortality and rendered this treatment feasible in elderly patients. The role of non-myeloablative allogeneic transplantation for multiple myeloma however, has not yet been defined. We have analyzed the results of patients with relapsed or refractory multiple myeloma treated at our institution. Between 08/1999 and 02/2004, 56 patients with relapsed (n=54) or refractory (n=2) myeloma were treated with non-myeloablative allogeneic transplantation. The median beta2microglobulin at the time of diagnosis was 2.75 mg/l, and median age at the time of transplant was 54.5 years (39.2–67.8). The median time from diagnosis to transplant was 3.6 years. Prior to allogeneic transplantation, patients received reinduction chemotherapy which included an autologous transplantation for 30 patients. The median number of previous cycles of conventional chemotherapy was 9. The conditioning regimen was 2 Gy TBI with (n=43) or without (n=3) fludarabin 3 x 30 mg/m² for 46 patients, the remaining 10 patients received a melphalan containing regimen. Acute toxicity was low with a WBC &lt; 500/μl and platelets &lt; 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved &gt; 90 % donor chimerism by day 56. Acute GvHD Grade II-IV occurred in 36 % of patients with 22 % Grade III-IV, and 61 % experienced chronic GvHD. Total transplant related mortality reached 20 %, with a day 100 TRM of 5 %. 32 patients experienced relapse or progressive disease, and 32 % of patients died due to relapse. The Kaplan-Meier estimate of overall survival and progression free survival at 18 months was 40 % and 25 %, respectively, with a median follow up of survivors of 21 months. Patients who experienced cGvHD had a significantly higher overall survival estimate (60 % vs. 20 % at 18 months, p=0.03). The number of cycles of pretreatment before allogeneic transplantation had a statistically significant negative influence on overall (p=0.02) and progression free survival (p=0.006). We conclude that non-myeloablative allogeneic transplantation is feasible in patients with relapsed multiple myeloma. The significant poor prognostic factors we identified were absence of chronic GvHD and number of cycles of pretreatment. Allogeneic transplantion should therefore be considered as an option earlier in the course of the disease.

scholarly journals Renal response in real-world carfilzomib- vs bortezomib-treated patients with relapsed or refractory multiple myeloma

2021 ◽  
Vol 5 (2) ◽  
pp. 367-376
Author(s):  
Shaji Kumar ◽  
Alan Fu ◽  
Ruben Niesvizky ◽  
Sundar Jagannath ◽  
Ralph Boccia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Positive Association ◽  
Complete Response ◽  
Rank Test ◽  
Renal Response ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Models ◽  
Rate Ratios

Abstract In the phase 3 ENDEAVOR study, carfilzomib-dexamethasone (Kd) improved survival over bortezomib-dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM), regardless of baseline renal function. This real-world study compared renal response in patients with RRMM (1-3 prior lines) and renal impairment (estimated glomerular filtration rate ≤50 mL/min) treated with Kd vs Vd. Electronic medical records data from the Oncology Services Comprehensive Electronic Records database were assessed (from January 2012 through February 2018). Time to renal response (defined according to International Myeloma Working Group criteria) was evaluated using the Kaplan-Meier method and log-rank test. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for renal overall response (ROR) and renal complete response (RCR) using Cox proportional hazard models adjusted for baseline covariates. Included were 543 Kd-treated and 1005 Vd-treated patients. In line 2 (2L), compared with Vd, Kd achieved significantly higher ROR (51.4% vs 39.6%; P &lt; .0001) and RCR (26.6% vs 22.2%; P = .0229). After baseline covariate adjustment, 2L patients receiving Kd vs Vd were 45% more likely to achieve ROR (IRR, 1.45; 95% CI, 1.18-1.78), and 68% were more likely to achieve RCR (IRR, 1.68; 95% CI, 1.24-2.28). The renal response benefit with Kd remained consistent in 2L to line 4 (4L). In a combined analysis of patients receiving Kd and Vd (2L and 2L-4L), renal responders had longer overall survival and time to next treatment than renal nonresponders. These results demonstrate improved real-world effectiveness of Kd over Vd in RRMM renal rescue, and the positive association between renal response and improved survival.

Real-world treatment patterns in relapsed/refractory multiple myeloma: Clinical and economic outcomes in patients treated with pomalidomide or daratumumab

2021 ◽  
pp. 107815522199553
Author(s):  
Joshua Richter ◽  
Vamshi Ruthwik Anupindi ◽  
Jason Yeaw ◽  
Suneel Kudaravalli ◽  
Stojan Zavisic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Treatment Options ◽  
Proteasome Inhibitors ◽  
Economic Outcomes ◽  
Office Visits ◽  
Refractory Multiple Myeloma ◽  
Kaplan Meier ◽  
Real World Evidence ◽  
New Treatment

Introduction Real-world evidence on later line treatment of relapsed/refractory multiple myeloma (RRMM) is sparse. We evaluated clinical outcomes among RRMM patients in the 1-year following treatment with pomalidomide or daratumumab and compared economic outcomes between RRMM patients and non-MM patients. Patient and Methods Adult patients with ≥1 claim of pomalidomide or daratumumab were identified between January 2012 and February 2018 using IQVIA PharMetrics® Plus US claims database. Patients were required to have a diagnosis or treatment for MM and a claim of any immunomodulatory drugs and proteasome inhibitors before the index date. Mean time to new therapy, overall survival (OS) using Kaplan-Meier curve and adverse events (AEs) were reported over the 1-year post-index period. RRMM patients were also matched to a non-MM comparator cohort and economic outcomes were compared between the two cohorts. Results 289 RRMM patients were matched to 1,445 patients without MM. Most prevalent hematological AE was anemia (72.0%) and non-hematological AE was infections (75.4%). Mean (SD) time to a new treatment was 4.7 (5.3) months and median OS was 14.6 months. RRMM patients had significantly higher hospitalizations and physician office visits (Both P < .0001) compared to non-MM patients. Adjusting for baseline characteristics, patients with RRMM had 4.9 times (95% CI 3.8-6.4, P < .0001) the total healthcare costs compared with patients without MM. The major driver of total costs among RRMM patients was pharmacy costs (67.3%). Conclusion RRMM patients showed a high frequency of AEs, low OS, and a substantial economic burden suggesting need for effective treatment options.

scholarly journals Clinical Relevance of Tubular Breast Carcinoma: Large Retrospective Study and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasna Metovic ◽  
Alberto Bragoni ◽  
Simona Osella-Abate ◽  
Fulvio Borella ◽  
Chiara Benedetto ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Meta Analysis ◽  
Analysis Data ◽  
Lymph Node Involvement ◽  
Rank Test ◽  
Control Series ◽  
Tubular Carcinoma ◽  
Excellent Outcome ◽  
Kaplan Meier ◽  
Node Involvement

Background: Tubular carcinoma (TC) is a low proliferative grade 1 (G1) breast cancer (BC). Despite its favorable outcome and allegedly lower aggressiveness, patients are treated like other luminal G1 BC, with radiotherapy (RT) and hormonal therapy (HT). We performed: (1) a retrospective study comparing a TC cohort and a control series of luminal G1 BC and (2) a systematic review and meta-analysis focused on TC outcome.Materials and Methods: We selected a series of 572 G1 luminal BC patients [111 TC, 350 not otherwise specified (NOS), and 111 special-type (ST) BC] with follow-up and clinico-pathological data, who underwent local excision followed by RT at Città della Salute e della Scienza Hospital, Turin. Moreover, 22 and 13 studies were included in qualitative and quantitative meta-analysis, respectively.Results: TCs were generally smaller (≤10 mm) (P &lt; 0.001), with lower lymph node involvement (P &lt; 0.001). TCs showed no local and/or distant recurrences, while 16 NOS and 2 ST relapsed (P = 0.036). Kaplan–Meier curves confirmed more favorable TC outcome (DFI: log-rank test P = 0.03). Meta-analysis data, including the results of our study, showed that the pooled DFI rate was 96.4 and 91.8% at 5 and 10 years, respectively. Meta-regression analyses did not show a significant influence of RT nor HT on the DFI at 10 years.Conclusions: Compared to the other G1 BCs, TCs have an excellent outcome. The meta-analysis shows that TC recurrences are infrequent, and HT and RT have limited influence on prognosis. Hence, accurate diagnosis of TC subtype is critical to ensuring a tailored treatment approach.

Daratumumab therapy for relapsed or refractory multiple myeloma: a single-center retrospective study

2020 ◽  
Vol 25 (12) ◽  
pp. 2151-2157
Author(s):  
Kazutaka Sunami ◽  
Hiroyuki Murakami ◽  
Hisashi Tagashira ◽  
Hiroko Ueda ◽  
Takashi Moriyama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Study ◽  
Single Center ◽  
Refractory Multiple Myeloma

scholarly journals Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability

Blood ◽  
2010 ◽  
Vol 115 (18) ◽  
pp. 3671-3677 ◽  
Author(s):  
Barbara Sarina ◽  
Luca Castagna ◽  
Lucia Farina ◽  
Francesca Patriarca ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Hodgkin Lymphoma ◽  
Autologous Transplantation ◽  
Multivariable Analysis ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Hla Typing ◽  
Human Leukocyte Antigen Typing ◽  
Leukocyte Antigen

Abstract Hodgkin lymphoma relapsing after autologous transplantation (autoSCT) has a dismal outcome. Allogeneic transplantation (alloSCT) using reduced intensity conditioning (RIC) is a salvage option, but its effectiveness is still unclear. To evaluate the role of RIC alloSCT, we designed a retrospective study based on the commitment of attending physicians to perform a salvage alloSCT; thus, only Hodgkin lymphoma patients having human leukocyte antigen-typing immediately after the failed autoSCT were included. Of 185 patients, 122 found an identical sibling (55%), a matched unrelated (32%) or a haploidentical sibling (13%) donor; 63 patients did not find any donor. Clinical features of both groups did not differ. Two-year progression-free (PFS) and overall survival (OS) were better in the donor group (39.3% vs 14.2%, and 66% vs 42%, respectively, P < .001) with a median follow-up of 48 months. In multivariable analysis, having a donor was significant for better PFS and OS (P < .001). Patients allografted in complete remission showed a better PFS and OS. This is the largest study comparing RIC alloSCT versus conventional treatment after a failed autoSCT, indicating a survival benefit for patients having a donor.

scholarly journals Serum Endocan as a Survival Predictor for Patients with Liver Cirrhosis

2015 ◽  
Vol 29 (8) ◽  
pp. 427-430 ◽  
Author(s):  
Nobuyuki Toshikuni ◽  
Kazuaki Ozaki ◽  
Joseph George ◽  
Mikihiro Tsutsumi
Keyword(s):  
Liver Cirrhosis ◽  
Proportional Hazards Model ◽  
Survival Rates ◽  
Elevated Serum ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Hepatic Decompensation ◽  
Cumulative Survival ◽  
Kaplan Meier ◽  
Survival Predictor

BACKGROUND: The relationship between endocan expression and outcome in patients with chronic liver disease is not fully understood.OBJECTIVE: To examine whether serum endocan level is predictive of outcome in patients with liver cirrhosis.METHODS: A total of 68 patients with liver cirrhosis were enrolled. Outcome predictors were analyzed using the Cox proportional hazards model. The overall survival rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test.RESULTS: During the median follow-up period (7.1 years), nine patients had hepatocellular carcinoma (HCC) and 10 patients died. Of the deceased patients, nine died due to hepatic decompensation or associated conditions. No significant factors were found to be predictive of the occurrence of HCC. In contrast, an elevated serum endocan level (≥2.0 ng/mL; HR 2.34 [95% CI 1.05 to 7.03]; P=0.037) and high Child-Pugh grade B/C (HR 2.65 [95% CI 1.30 to 6.89; P=0.006) were predictive of poor survival. Kaplan-Meier analysis revealed that the respective cumulative survival rates at five and 10 years were 97.1% and 87.4% in patients with serum endocan levels <2.0 ng/mL and 85.8% and 64.4% in patients with levels ≥2.0 ng/mL (P=0.009), respectively. Moreover, the cumulative survival rates were significantly different among the patient groups divided according to serum endocan level and Child-Pugh grade (P=0.002).CONCLUSION: These findings suggest that serum endocan level may be a survival predictor for patients with liver cirrhosis.

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