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  • 11
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5625-5625
    Abstract: Background: Management of relapsed or refractory multiple myeloma (RRMM) is challenging. Venetoclax (ABT-199) is an oral selective inhibitor of an anti-apoptotic protein Bcl-2 that showed activity in preclinical studies, especially for t(11;14) MM cell lines or in the cells with high bcl-2 expression. We conducted a systematic review and meta-analysis to evaluate the outcomes of venetoclax in RRMM. Method: Literature databases (Medline, Embase, and Cochrane) were searched for studies published up to June 19, 2018. Our search strategy included MeSH terms and key words for multiple myeloma and venetoclax including trade names and generic names. CMA software v.3 was used for analysis. Random-effects model was applied. Results: 163 patients (n=115 in dose escalation, n=48 in safety expansion) were identified from two clinical trials (phase Ib study by Moreau, P. et al. 2017, n=66 and phase I/II study by Kumar, S. et al. 2017, n=66) and one retrospective study (Galligan, D. et al. 2017, n=31). The median age was 63, 64, N/A in phase Ib, phase I/II and retrospective study, respectively. 47 patients (29%) had t(11;14). Other cytogenetic aberrations were del(17p) [n 〈 25]; t(4;14) [n=5] ; del(13q) [n=41]; t(14;16) [n 〈 5]; t(14;20) [n 〈 5]. 124 patients (76%) were refractory to bortezomib and/or lenalidomide; most patients had ≥3 prior therapies. Venetoclax doses escalated from 50 mg/day to 1200 mg/day in phase Ib and phase I/II studies. Safety expansion doses were 800 mg and 1200 mg in phase Ib and phase I/II studies, respectively. Median dose of venetoclax for the retrospective study was 800 mg daily. Bortezomib and dexamethasone doses from phase Ib study were 1.3 mg/m2 subcutaneous and 20 mg, respectively. The median duration on venetoclax and median time on study ranged from 2 to 6 months. Median duration of response (DOR) and median time-to-progression (TTP) were reported higher with combination therapy of bortezomib and dexamethasone (9.7 months and 9.5 months, respectively). 62% of patients have discontinued the therapy due to: progressive disease (48%), adverse events (6%), and various other reasons (8%). There were 13 deaths; 6 were due to disease progression. Most common side effect from three studies was gastrointestinal problems such as nausea, diarrhea and vomiting. The median duration of response was 9.7, 9.7, 2 months and the median time to progression was 9.5, 2.6, NA months for phase Ib, phase I/II and retrospective study, respectively. The pooled overall response rate (ORR) for all patients was 43% (n=163) with the highest rate (67%) being reported from phase Ib study using combined venetoclax, bortezomib and dexamethasone (Figure 1 and 2). Among 44 patients with t(11;14), ORR was 40% and 78% in phase I/II and phase Ib studies, respectively. Twenty-eight patients who expressed high-bcl2 showed ORR rates of 80% and 94%, whereas 50 patients who had low-bcl2 level showed ORR rates of 8% and 59% in phase I/II and phase Ib studies, respectively (Table 1). Conclusion: Single-agent venetoclax showed an ORR of 21%, the addition of bortezomib produced an ORR of 32%, and the addition of bortezomib and dexamethasone improved an ORR to 67%. Better ORR was observed in patients with t(11;14) and with high-bcl2 expression. The highest median DOR (9.7 months) and TTP (9.5 months) were reported with a combination therapy of venetoclax, bortezomib and dexamethasone. Most reported adverse events were related to gastrointestinal system. More clinical studies evaluating the combination therapies using venetoclax are needed. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 12
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5559-5559
    Abstract: Background: For most of the elderly or unfit CLL patients, treatment algorithms focus on achievement of clinical response, relief of symptoms and prolongation of life expectancy. Comorbidities, frailty and reduced functional status in elderly patients make some of the standard treatments intolerable and less efficacious. However, recent advancements in understanding of CLL biology, approval of target agents including novel monoclonal antibodies and kinase inhibitors have expanded the horizons for treatment of CLL in elderly. Methods: We conducted a literature search on PubMed, Embase, Web of Science and ClinicalTrials.gov which was completed on July 1, 2018. To assess the CLL treatment protocols in the elderly population, we included data from phase II and phase III clinical trials from the last decade (Jan 2008 to Jan 2018). Results: From a total of 1259 studies, we selected 34 studies (n=3122) after inclusion criteria were met. The patients included are from the age group of ≥65 years with the mean age of 68.8 years. Male to female ratio was 3:2. On comparison of different parameters to look for the drug or regimen efficacy, we found that ibrutinib is very effective and tolerable in older (aged ≥65 years) treatment-naïve (TN) as well as relapsed refractory patients (RR), with overall response rate (ORR) of 91% for combined group in one study when compared to ofatumumab. When used in combination with ublituximab, the ORR peaked to 80% as compared to ibrutinib alone in patients with high risk cytogenetics (ORR=47%, p 〈 0.001). Phase III RESONATE trial showed a comparison between ibrutinib and chlorambucil treated del 17p negative elderly patients; ibrutinib was superior in terms of ORR (86% vs. 35%) and overall survival (OS) (2-year OS, 98% vs. 85%, p=0.001). The OS with ibrutinib turned out to be 89% showing better disease control as compared to idelalisib (OS= 61%) when used in combination with rituximab, with a 33% reduction in mortality with ibrutinib as compared with idelalisib in RR patients. The combination of rituximab with idelalisib has shown promising results in patients with specific mutations (i.e. 100% ORR in those with del (17)/ Tp53 mutations, 97% ORR in those with unmutated IGHV). Similarly, when compared with placebo and rituximab combination progression free survival (PFS) was 13%, idelalisib is found to have PFS of 66% at 12 months in patients with del 17p/ Tp53 mutations and unmutated IGHV status. Moreover, in a phase II study, ofatumumab monotherapy showed ORR of 72%. In newly diagnosed (ND) CLL, an ORR of 98% is found with the pentostatin, cyclophosphamide, rituximab, and lenalidomide regimen. Other worth sharing results include; complete remission (CR) in 71% (24 out of 34 included) patients who were given lenalidomide as an initial therapy, with OS of 88% and ORR of 65%. The OS is surprisingly as high as 97.9% in those who were given pentostatin and cyclophosphamide in combination with ofatumumab. Traditional chemotherapy with fludarabine and rituximab (FR) showed OS of 67% in one study with rates of grades II and III-IV acute GVHD as 60% and 15% respectively. The most common hematological side effects seen with ibrutinib in one of the studies are neutropenia (12%), thrombocytopenia (4%) and anemia (7%). The non-hematological complications may be secondary due to cytopenias (infections, pneumonia, bleeding, and neutropenic fever) or due to constitutional symptoms like myalgia, fatigue, vomiting, or nausea. Conclusion: The rapid clinical development of novel therapy agents has changed the prognosis for CLL patients. Ibrutinib is considered as a standard option and an up front therapy for high risk CLL patients especially who are elderly and have del 17p, despite its significant toxicity profile in very elderly patients (80 years and above) where multiple deaths were reported. Future prospects include ibrutinib combinations with frontline chemo-immunotherapy (CIT) and other novel agents for TN and RR del 17p negative patients. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 13
    In: Gastroenterology, Elsevier BV, Vol. 160, No. 6 ( 2021-05), p. 2055-2071.e0
    Type of Medium: Online Resource
    ISSN: 0016-5085
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 14
    In: Acta Radiologica, SAGE Publications
    Abstract: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. Purpose To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m ( 99m Tc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. Material and methods Radiolabeling of FLUT with 185 MBq freshly eluted 99m TcO 4 −1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. Results Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed 〉 95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [ 99m Tc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [ 99m Tc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. Conclusion Stable, newly developed [ 99m Tc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.
    Type of Medium: Online Resource
    ISSN: 0284-1851 , 1600-0455
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    Language: English
    Publisher: SAGE Publications
    Publication Date: 2024
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  • 15
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5629-5629
    Abstract: Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 16
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5768-5768
    Abstract: Background: The use of peripheral blood stem cell source (PBSC) continues to grow in the setting of haploidentical hematopoietic stem cell transplantation (haplo-SCT), mainly due to the ease of collection and rapid peripheral blood count recovery. We conducted a systematic review and meta-analysis of the published literature to evaluate the outcomes of unmanipulated bone marrow (BM) and PB haplo-SCT for adult leukemia patients. Method: A comprehensive literature search of electronic databases (Medline, Embase, and Cochrane library) for studies published between 1 January 2004 to 24 June 2018 was conducted. We included the studies of unmanipulated BM and/or PB haplo-SCT in adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia ( ALL) . We excluded the studies which combined PB and BM stem cell sources and the studies which did not report the results of BM and PB haplo-SCT for ALL and AML separately. CMA software v.3 was used for the analysis. Heterogeneity among studies was assessed using the I2 test. Random-effect model was applied. Publication bias was assessed using funnel plots. Primary endpoints were engraftment, 2-year overall survival (OS), disease-free survival (DFS), relapse incidence (RI); grade II-IV, III-IV acute and chronic GVHD. Results: Out of 1548 publications, 3 studies (n = 672 patients; retrospective; multi-center) met our inclusion criteria. The sample size of the studies varied between 71 and 451 patients. The median follow-up ranged from 18 to 46 months. PB haplo-SCT was used in 191 patients (Ruggeri, A. et al. 2018) and BM haplo-SCT was used in 481 patients (Arcese, W. et al. 2015; Ruggeri, A. et al. 2018; Chiusolo, P. et al. 2018). Myeloablative (MA) conditioning was used in majority of patients. The pooled (95%CI) engraftment rate was 93% (88-95) in BM group and 95% (91-97) in PBSC group. The pooled estimates (95%CI) of BM studies showed a 2-year OS rate of 56.1% (51.6-60.4), 2-year DFS of 48.9% (43.5-54.2) and 2-year cumulative RI of 24.6%(20.7-29).There was no heterogeneity in BM group (I2=0%) for 2-year OS, DFS and RI. For PBSC group, the pooled estimates (95%CI) for 2-year OS, DFS and RI were 56 % (48.9-62.9; I2=0%), 54% (46.9-60.9; I2=0%) and 22% (16.7-28.4; I2=0%), respectively. Incidences of grade II-IV, grade III-IV aGVHD and cGVHD from a pooled analysis (95%CI) were 23.1% (17.2-30.3; I2=55%), 5.4% (3.4-8.3; I2=16%) and 19.5% (9.7-35.3; I2=88%) for BM group in comparison to 38% (31.4-45.1; I2=0%), 14% (9.8-19.7; I2=0%) and 32% (25.8-38.9; I2=0%) for PBSC group. Pooled estimates were shown in figure 1. Conclusions: In this analysis, higher pooled rates of grade II-IV aGVHD (38% vs 23.1%), III-IV aGVHD (14% vs 5.4%) and cGVHD (32% vs 19.5%) were observed in PBSC group vs BM group, respectively. Based on comparable OS, DFS and RI, PB haplo-SCT appears to be a good alternative option for adult AML and ALL patients. Large prospective randomized controlled trials are required to confirm these results. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 17
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1952-1952
    Abstract: Introduction: Multiple myeloma (MM) is associated with end organ damage that negatively impacts the quality of life (QOL)and supportive care has a potential to improve symptoms. Methods: After detailed search on Pubmed, Cochrane, Embase and Clinical Trials.gov, we finalized total 36 articles on supportive care published after 2004. Results: Management of skeletal events: Mhaskar et al. (2017, n=3257) compared bisphosphonates (BPs) with placebo (PBO) in preventing pathological vertebral fractures, skeletal-related events (SRE), reported risk ratio (RR) of 0.74 in each; 95% CI 0.62-0.89 and 0.63-0.88 respectively. Both zoledronic acid (ZA) and clodronic acid prevent SRE, but mortality rate was better reduced with ZA (hazard ratio [HR]=0.84; p=0.0118), (Gareth et al. 2010, n=1960). In a study by Zuradelli et al. (2009, n= 240); hypocalcemia developed in 93 (38.8%) patients on ZA for a median of 2.3 months (range, 0-34.9). Vitamin D and calcium replacement is essential in patients developing hypocalcemia with BPs, (Kennel et al. 2009). Vertebral augmentation procedures improved pain after compression fracture (n=923) by 4.8, 4.6 and 4.4 points at 1 week, 1 year and beyond 1 year respectively, (Khan et al. 2014). Valerie et al. (2011, n=84) analyzed improvement in bone pain with radiotherapy (median 45 grays) in 92 % patients. Prophylaxis of infections: Leng et al. (2018, n=70,687) observed reduced risk of herpes zoster (HZ) reactivation in patients on bortezomib or carfilzomib + HZ prophylaxis (2.4%) vs 5.8% in non-prophylactic group, (attributable risk reduction: 0.42; 95% CI 0.31-0.56). Teh et al. (2016, n=199) reported reduced risk of varicella zoster virus reactivation with valacyclovir (500 mg) in patients on bortezomib based therapy and following autologous stem cell transplant (ASCT) vs no prophylaxis (HR=0.06 vs 16.9; p 〈 0.01). Dimopoulos et al. (2016, n=569) found higher risk of pneumonia, 8.2% in daratumumab group (n=286) vs 7.8% in control group (n=283). Prophylactic trimethoprim-sulfamethoxazole reduced risk of PCP in 85% patients after ASCT (RR=0.15; 95% CI 0.04-0.62), Stern et al. (2014, n=1000). Incidence of Community-acquired pneumonia (CAP), noninvasive CAP and invasive pneumococcal disease in elderly population (≥65 years) was seen in 49, 33 and 7 patients on Pneumococcal polysaccharide conjugate vaccine group as compared to 90, 60 and 28 patients in placebo group respectively, (Bonten et al. 2015, n=84,496). Role of plasmapheresis in renal impairment (RI): Alkhatib et al. (2017) showed that plasmapheresis reduced dialysis dependency by removing serum free light chains (sFLC) in patients with RI (n=147), (RR 0.45; P = 0.02). Yu-X et al. (2015, n=147), showed lower 6-month dialysis dependency ratio with plasmapheresis and chemotherapy (PP + CTH) vs CTH alone, (15.6% vs 37.2%; RR=2.02; p = 0.04). High cut-off hemodialysis lowered sFLC level in 61% (n=42) and 63% patients at day 12 and 21 respectively. Out of these, 71% and 69% patients became dialysis independent, (Hutchison et al. 2012, n=67). Peripheral neuropathy (PN): Bortezomib caused PN in 124/331 (37%) patients (Richardson et al. 2009) whereas with thalidomide, the incidence of PN was 38% and 73% at 6 and 12 months, respectively, (Mileshkin et al. 2006, n=75). PN improved in 68% patients on bortezomib with dose modifications (n=72) vs 47% patients, without dose modification (n=19). (Table 1 and 2). Significant improvement in PN was seen with duloxetine vs placebo (1.06 vs. 0.34; p= 0.003), (Smith et al. 2013, n=231). Arbaiza et al. (2007, n=36) showed improvement in neuropathic pain with tramadol (p= 〈 0.001). Epoetin and derivates for anemia: Castelli et al. (2017, n= 31; median creatinine 1.2 mg/dL (0.8-3.0)) reported hemoglobin (Hb) increase of ≥1g/dL and ≥2g/dL in 71% and 31.7% patients respectively with epoetin α, transfusions requirement reduced from 2.39 ± 1.05 to 1.23 ± 1.36 (p 〈 0.001). Begiun et al. (2013, n= 72) compared the effect of darbepoetin (D) ± iron (Fe) vs placebo on erythroid recovery after ASCT. All patients receiving D + Fe achieved Hb ≥13 g/dL (p 〈 0.0001). Tonia et al. (2012, n= 16,093) showed 35% decrease in transfusion need with erythropoietin stimulating agents (RR=0.65; 95% CI 0.62-0.68). (Table 3) Conclusion: Along with anti-myeloma chemotherapy therapy, management of complications (anemia, infections, renal insufficiency) and other associated symptoms is necessary to improve the quality of life. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 18
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3239-3239
    Abstract: Introduction: Survival of patients with multiple myeloma (MM) has improved over the last decade, mainly due to advent of newer drugs, three drug based induction, high dose chemotherapy consolidation and routine use of maintenance therapy for eligible patients. Despite advances in therapy, many cases of MM ultimately relapse and there is need to summarize evidence comparing efficacy and clinical outcome of combination regimens used in relapsed or refractory MM (RRMM) treatment. We performed a systematic review and meta-analysis of randomized controlled trials to compare the efficacy of lenalidomide based three drug regimens versus two drug regimens among relapsed and refractory myeloma (RRMM) patients. Methods: We conducted a literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov which was completed on March 26, 2018. We used keywords like "relapsed multiple myeloma", "revlimid", "dexamethasone", "elotuzumab", "carfilzomib", "bortezomib", "ixazomib", "daratumumab", "doxorubicin", "pembrolizumab", "thalidomide", "cyclophosphamide" along with MeSH and Emtree terms. The primary meta-analytic approach was a random effects model using the Mantel-Haenszel method. It was used to calculate pooled risk ratio of objective response rates with 95% confidence interval. Cochrane Collaboration's tool was used for quality assessment of included studies. Systematic reviews, meta-analyses, combination regimen without lenalidomide, newly diagnosed MM patients, and other plasma cell dyscrasias were excluded. Results: Literature search retrieved 11,362 titles. Following initial screening, 72 articles were considered for full text review. Of these only five studies with 2844 patients met inclusion criteria and two studies qualified for meta-analysis. The study arm used daratumumab (Dara), ixazomib, carfilzomib, or elotuzumab in combination with lenalidomide (Len) and dexamethasone (Dex). The control arm used combination of Len and Dex (LenD). There was no difference in overall response rate (ORR) between ixazomib-Len-Dex regimen versus LenD (RR=1.33, 95% CI = 0.83 to 2.17, p= 0.236). However significantly higher complete response (CR) was observed in ixazomib-Len-Dex group compared to LenD (RR = 1.82, 95% CI = 1.14 to 2.93, p = 0.013). An absolute increase in ORR among carfilzomib-Len-Dex, elotuzumab-Len-Dex, and daratumumab-Len-Dex versus LenD was 20.4% (87.1% vs. 66.7%, p 〈 0.001), 13% (79% vs 66%, p 〈 0.001) and 16.5% (92.9% vs. 76.4%, p 〈 0.001) respectively. Conclusion: Daratumumab and carfilzomib in Len based three drug regimens have better clinical efficacy when compared to lenalidomide and dexamethasone based two drug regimens among relapsed and refractory multiple myeloma patients. There was no difference between the ORR of ixazomib based combination regimen and LenD but higher number of patients achieved deeper responses. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 19
    In: The American Journal of Cardiology, Elsevier BV, Vol. 204 ( 2023-10), p. 168-170
    Type of Medium: Online Resource
    ISSN: 0002-9149
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2019595-3
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  • 20
    In: Cell, Elsevier BV, Vol. 171, No. 6 ( 2017-11), p. 1259-1271.e11
    Type of Medium: Online Resource
    ISSN: 0092-8674
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 187009-9
    detail.hit.zdb_id: 2001951-8
    SSG: 12
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