Kooperativer Bibliotheksverbund

In: The Lancet Haematology, Elsevier BV, Vol. 9, No. 11 ( 2022-11), p. e810-e821

Type of Medium: Online Resource

ISSN: 2352-3026

URL: Article

DOI: 10.1016/S2352-3026(22)00263-0

Language: English

Publisher: Elsevier BV

Publication Date: 2022

In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 29, No. 1 ( 2023-01-04), p. 279-288

Abstract: Proteasome inhibitors (PI) are the backbone of various treatment regimens in multiple myeloma. We recently described the first in-patient point mutations affecting the 20S subunit PSMB5 underlying PI resistance. Notably, in vivo, the incidence of mutations in PSMB5 and other proteasome encoding genes is too low to explain the development of resistance in most of the affected patients. Thus, additional genetic and epigenetic alterations need to be explored. Experimental Design: We performed DNA methylation profiling by Deep Bisulfite Sequencing in PSMB5, PSMC2, PSMC5, PSMC6, PSMD1, and PSMD5, a subset of proteasome subunits that have hitherto been associated with PI resistance, recruited from our own previous research, the literature, or a meta-analysis on the frequency of somatic mutations. Methylation was followed up on gene expression level and by dual-luciferase reporter assay. The KMS11 cell line served as a model to functionally test the impact of demethylating agents. Results: We identified PSMD5 promoter hypermethylation and subsequent epigenetic gene silencing in 24% of PI refractory patients. Hypermethylation correlated with decreased expression and the regulatory impact of this region was functionally confirmed. In contrast, patients with newly diagnosed multiple myeloma, along with peripheral blood mononuclear cells and CD138+ plasma cells from healthy donors, generally show unmethylated profiles. Conclusions: Under the selective pressure of PI treatment, multiple myeloma cells acquire methylation of the PSMD5 promoter silencing the PSMD5 gene expression. PSMD5 acts as a key orchestrator of proteasome assembly and its downregulation was described to increase the cell's proteolytic capacity. PSMD5 hypermethylation, therefore, represents a novel mechanism of PI tolerance in multiple myeloma.

Type of Medium: Online Resource

ISSN: 1078-0432 , 1557-3265

URL: Article

DOI: 10.1158/1078-0432.CCR-22-1161

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2023

detail.hit.zdb_id: 1225457-5

detail.hit.zdb_id: 2036787-9

In: Blood Cancer Journal, Springer Science and Business Media LLC, Vol. 9, No. 2 ( 2019-01-29)

Abstract: Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.

Type of Medium: Online Resource

ISSN: 2044-5385

URL: Article

DOI: 10.1038/s41408-019-0174-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2600560-8

In: Leukemia, Springer Science and Business Media LLC, Vol. 33, No. 1 ( 2019-1), p. 258-261

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-018-0195-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2008023-2

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3373-3373

Abstract: Introduction: The German-Speaking Myeloma Multicenter Group (GMMG) has initiated a randomized multicenter phase III trial on the effect of elotuzumab in VRD (bortezomib, lenalidomide, dexamethasone) induction/consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (GMMG-HD6 trial, NCT02495922). The study compares four cycles induction therapy with VRD vs. VRD + elotuzumab, followed by standard intensification (i.e. mobilization and stem cell transplantation), two cycles consolidation with VRD/VRD + elotuzumab and lenalidomide maintenance +/- elotuzumab. The primary endpoint is determination of the best of four treatment strategies regarding progression-free survival. Here we present a first analysis of stem cell mobilization within this study. Patients and Methods: We performed a retrospective analysis of collection data on all patients who underwent peripheral blood stem cell (PBSC) collection between trial initiation in June 2015 and June 2016. Only patients with completely available datasets in respect of mobilization were considered (n=111). The vast majority of 99 patients (89%) received chemomobilization with CAD (cyclophosphamide, adriamycin, dexamethasone) followed by 5-10 µg G-CSF /kg body weight (bw) /d (starting day +9 until completion of PBSC collection), while in one case (1%) dexamethasone was omitted and in 10 cases (9%) cyclophosphamide mono was administered. One patient underwent steady-state mobilization with G-CSF only (10µg /kg bw /d). 55/111 patients received VRD (50%), whereas the remaining patients received VRD + elotuzumab. According to the recommendations of the study group, PBSCs for three stem cell transplants were to be collected. One transplant ideally consisted of ≥2.5 x10^6 CD34+ cells /kg bw, but in the event of poor mobilization as low as ≥2.0 x10^6 CD34+ cells /kg bw would be considered acceptable. Results: The median number of collected CD34+ cells was 10.4 x10^6 /kg bw (range 2.88 to 23.01 x10^6 /kg bw). Overall, 92 patients (83%) collected ≥7.5 x10^6 CD34+ cells /kg bw and another 12 patients (11%) collected between 6.0 and 7.5 x10^6 CD34+ cells /kg bw, resulting in three transplants, respectively. Only 7 patients (6%) collected below 6.0 x10^6 CD34+ cells /kg bw; 5 of them had been treated in the VRD-arm without elotuzumab. Due to insufficient PBSC mobilization after conventional treatment, 14 patients (13%) received a rescue mobilization with plerixafor, from which 12 patients collected ≥6.0 x10^6 CD34+ cells /kg bw. Overall, 7 serious adverse events (SAEs) occurred during mobilization phase, 4 of them in the study arm with elotuzumab. Conclusions: Cyclophosphamide-based chemomobilization after induction therapy with VRD is feasible. Efficient PBSC collection of ≥6.0 x10^6 CD34+ cells /kg bw could be performed in 104 of 111 patients (94%), with a low incidence of SAEs. The need for rescue mobilization was not higher than that of comparable previous GMMG treatment protocols. The addition of elotuzumab during induction phase did not impede PBSC collection. Disclosures Wuchter: Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bertsch:Janssen: Research Funding; Celgene: Research Funding; Chugai: Research Funding. Munder:Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Fenk:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Hillengass:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Research Funding; Sanofi: Research Funding. Raab:Novartis: Consultancy, Research Funding; BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ho:Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid:Medac: Other: Travel, accomodations or expenses; Baxalta: Honoraria; Amgen: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel, accomodations or expenses; Janssen: Consultancy, Honoraria; Celgene: Other: Travel, accomodations or expenses; BMS: Consultancy, Honoraria. Weisel:Onyx: Consultancy; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Goldschmidt:Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.3373.3373

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Hematological Oncology, Wiley, Vol. 36, No. 1 ( 2018-02), p. 210-216

Abstract: The histone deacetylase inhibitor panobinostat has shown efficacy in phase‐II and phase‐III trials for multiple myeloma and has recently received market approval in combination with bortezomib and dexamethasone. Here, we retrospectively report our single center experience with panobinostat/bortezomib/dexamethasone (FVD) in a heavily pretreated patient population (n = 24) with a high degree of refractoriness to proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Median age was 67 years (range 49‐87) and the median number of prior therapies was 5 (range 2‐17). Fourteen patients (58%) had high‐risk cytogenetic aberrations. Thirteen (54%) and 21 (88%) patients were refractory to PIs and IMiDs, respectively. Twelve patients (50%) were refractory to bortezomib and 7 (29%) to carfilzomib; 6 patients (25%) were refractory to both bortezomib and carfilzomib. In 21 patients evaluable for response, overall response rate (ORR; ≥PR) was 33% (7/21) and 81% (17/21) achieved at least stable disease. Median progression‐free survival (PFS) and overall survival were 3.5 and 9.8 months, respectively. Significant differences between bortezomib‐sensitive and ‐refractory patients were observed. In bortezomib‐sensitive patients, median PFS was 6.3 months compared to 2.3 months in bortezomib‐refractory patients ( P   〈  .001). Median overall survival was not reached vs 4.8 months ( P  = .046) in bortezomib‐sensitive and bortezomib‐refractory patients, respectively. The only patient refractory to carfilzomib but sensitive to bortezomib achieved very good partial remission and PFS of 6.3 months, suggesting discrete mechanisms of resistance to different PIs. As expected, thrombocytopenia and fatigue/asthenia occurred in nearly all patients (96% and 83%, respectively). Diarrhea was observed in only 19% of patients which compares favorably with the high rates of diarrhea reported in the PANORAMA trials. With panobinostat dose reductions in 67% of patients, FVD was tolerated by the majority of patients. In conclusion, FVD showed efficacy in a heavily pretreated, high‐risk multiple myeloma population with a high degree of patients refractory to novel agents including PIs.

Type of Medium: Online Resource

ISSN: 0278-0232 , 1099-1069

URL: Issue

URL: Article

DOI: 10.1002/hon.v36.1

DOI: 10.1002/hon.2462

Language: English

Publisher: Wiley

Publication Date: 2018

detail.hit.zdb_id: 2001443-0

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 17, No. 1 ( 2017-02), p. e120-

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/j.clml.2017.03.218

Language: English

Publisher: Elsevier BV

Publication Date: 2017

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 253-253

Abstract: Introduction Salvage high dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is used in fit patients with relapsed multiple myeloma (RMM) in clinical practice. However, the role of this approach in the era of continuous novel agent based treatment has not been defined in randomized trials. The ReLApsE trial compared lenalidomide/dexamethasone (Rd) re-induction, salvage HDCT/ASCT and lenalidomide (R) maintenance with standard continuous Rd in a randomized controlled multicenter trial. Methods Between 2010 and 2016, 282 patients were randomized of whom 277 constituted the intention-to-treat (ITT) population (arm B/A n=139/138). Arm B received 3 cycles of Rd (lenalidomide 25 mg, day 1-21; dexamethasone 40 mg, day 1, 8, 15, 22; 4 week cycles) re-induction, HDCT (melphalan 200 mg/m2), ASCT and R maintenance (10 mg daily) until progression (PD). Arm A was treated with Rd until PD. In both arms stem cells were harvested after the 3rd Rd cycle if no back-up transplant was available. Key inclusion criteria were 1-3 prior therapy lines, age ≤ 75 years, time to PD ≥ 12 months in case of front-line HDCT/ASCT and WHO PS ≤ 2. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall survival (OS), response rates and toxicity. ISRCTN16345835, Eudra CT-No: 2009-013856-61. Results Arm B and A were balanced regarding age (median 61.3 vs. 62.2 years), ISS (I/II/III in 62.6/24.4/13% vs. 59.7/31/9.3%) and WHO PS (0/1/2 in 69.1/30.9/0% vs. 76.1/23.2/0.7%). Almost all patients had only 1 prior therapy line (arm B: 94.2% vs. arm A: 93.5%) and had received front-line HDCT/ASCT (92.8% vs. 94.2%). More patients in arm B had high risk cytogenetic aberrations (HR-CA; 42.9% vs. 31.6%) based on a higher frequency of t(4;14) (20.2% vs. 10.1%). The overall response rate (≥ partial response; ORR) for arm B and A was 77.9% and 74.6% (p=0.57) with 49.3% and 47.1% (p=0.81) achieving ≥ very good partial response as best response. Within a median follow up of 36.3 months, 183 PFS events and 76 deaths occurred. Median PFS in the ITT population was 20.7 months in arm B and 18.8 months in arm A without a statistically significant difference (HR 0.87; 95% CI 0.65-1.16; p=0.34). Median OS was not reached (NR) in arm B vs. 62.7 months in arm A (HR 0.81; 95% CI 0.52-1.28; p=0.37). In arm B, 41 patients (29.5%) did not receive the planned HDCT/ASCT. Thus, exploratory landmark (LM) analyses from HDCT and the contemporaneous Rd cycle 5 in arm A were performed (median interval from randomization to HDCT/Rd cycle 5: 117/122 days; n=103[B]/114[A] ). They showed a trend towards superior PFS (23.3 vs. 20.1 months; HR 0.74; p=0.09) and significantly superior OS (NR vs. 57 months; HR 0.56; p=0.046) in arm B vs. A. Multivariate analyses revealed significant associations of treatment in arm B with superior LM PFS (HR 0.6; p=0.01) and LM OS (HR 0.39; p=0.006). Other factors in the LM multivariate models showing significant associations with survival were HR-CA (PFS, OS), number of prior therapy lines (PFS), and age (PFS). The ORR in arm B after HDCT/ASCT was significantly higher than in arm A after Rd cycle 5 (82.3% vs. 69.6%; p=0.04). Grade ≥3 adverse events were reported in 83% (arm B) and 74.5% (arm A; p=0.11). Grade ≥3 leukopenia/neutropenia was reported in 61.5 vs. 24.8% (p 〈 0.001), grade ≥3 thrombopenia in 45.2 vs. 11% (p 〈 0.001) and grade ≥3 mucositis in 10.4% vs. 2.1% (p=0.005). No significant difference in grade ≥3 infections/infestations (33.3 vs. 27.6%; p=0.3) was observed. Eleven patients died on protocol treatment (B: 4 vs. A: 7). No deaths occurred in the HDCT/ASCT phase. Conclusions This is the first RCT comparing salvage HDCT/ASCT with continuous novel agent based treatment. No significant PFS or OS difference was observed in the overall trial population. However, HR-CA were more frequent in the HDCT/ASCT arm and ~30% of patients did not receive the planned HDCT/ASCT. Landmark analyses from the time of HDCT indicate superior PFS and OS in patients actually undergoing salvage HDCT/ASCT. Salvage HDCT/ASCT was safe with an expected increase in hematological as wells as gastrointestinal toxicity but without treatment-related mortality in patients up to the age of 75 years in this multicenter trial. However, the number of patients not undergoing salvage HDCT/ASCT and the approval of more active Rd-based triplet regimens after the initiation of this trial prevents definite conclusions on the role of salvage HDCT/ASCT. Disclosures Goldschmidt: Amgen: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; ArtTempi: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Mundipharma: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Adaptive Biotechnology: Consultancy; Chugai: Honoraria, Research Funding. Baertsch:Takeda: Consultancy; Novartis: Consultancy, Research Funding. Raab:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Hillengass:Novartis: Honoraria, Other: Advisory Board; Sanofi: Research Funding; Takeda: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; amgen: Consultancy, Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Celgene: Consultancy, Honoraria, Other: Advisory Board, Research Funding. Graeven:AbbVie: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees. Fenk:Takeda: Honoraria; Bristol-Meyers Squibb: Honoraria, Other: travel grant; Celgene: Honoraria, Other: Travel grant, Research Funding; Janssen: Honoraria; Amgen: Honoraria. Haenel:Novartis: Honoraria; Roche: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Scheid:Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; BMS: Honoraria; Amgen: Honoraria. Salwender:Celgene: Honoraria, Other: travel suppport, Research Funding; Janssen: Honoraria, Other: travel support, Research Funding; Novartis: Honoraria, Other: travel suppport, Research Funding; Takeda: Honoraria; Amgen: Honoraria, Other: travel suppport, Research Funding; Bristol-Myers Squibb: Honoraria, Other: travel suppport, Research Funding. Weisel:Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-111203

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5686-5686

Abstract: The histone-deacetylase inhibitor panobinostat (PAN) has shown efficacy in phase II and III trials for multiple myeloma (MM) and has recently been approved in combination with bortezomib (BTZ) and dexamethasone (DEX) for the treatment of MM patients with at least two prior lines of therapy including BTZ and an immunomodulatory agent (IMiD). Here we retrospectively report our single center experience with PAN/BTZ/DEX (FVD) in a heavily pretreated patient population (n=24) with a high degree of proteasome inhibitor (PI) and IMiD refractoriness. Patients were treated starting from October 2015. The median age at treatment initiation was 67 years (range 49-87) and the number of prior lines of treatment was 5 (range 2-17) with a median interval from initial diagnosis of 6.3 years (range 2.1-15.2). Fourteen patients (58%) had high risk cytogenetic aberrations (del17p, t4;14, t14;16, +1q [ 〉 3 copies]) according to fluorescence in situ hybridization diagnosed at any time before FVD initiation and 11 of 20 patients (55%) evaluable for ISS at diagnosis had stage II/III disease. PI and IMiD refractoriness was present in 13 (54%) and 21 (88%) patients, respectively. Twelve patients (50%) were refractory to BTZ and 7 (29%) to carfilzomib (CFZ); 6 patients (25%) were double refractory to BTZ and CFZ. However, only 2 (8%) and 3 (13%) had received BTZ or CFZ, respectively, as part of their last line of therapy before FVD. In 22 evaluable patients, overall response rate (≥ PR; ORR) was 32% (7 of 22) and clinical benefit rate (≥ MR; CBR) was 50% (11 of 22). The median progression free survival (PFS) in the overall population was 3.3 months with median overall survival (OS) immature for reporting. Marked differences between BTZ sensitive and BTZ refractory patients were observed. ORR was 64% (7 of 11) vs. 0% (0 of 11) and CBR was 73% (8 of 11) vs. 36% (4 of 11), respectively; 73% (8 of 11) of the BTZ refractory patients achieved at least SD. Median PFS was 6.3 vs. 1.7 months and median OS immature vs. 5.1 months in BTZ sensitive and BTZ refractory patients, respectively. Interestingly, the only patient refractory to CFZ but sensitive to BTZ (6 prior lines of therapy) achieved VGPR and PFS of 6.3 months, suggesting discrete mechanisms of resistance to different PIs. Fatigue/asthenia was reported by 82% of patients and was mainly CTCAE grade 2 (52%); however, 3 patients had grade 3 fatigue/asthenia with reduced fluid intake resulting in deterioration of renal function, reduced vigilance and inpatient admission. Thrombopenia occurred in 96% and was mainly CTCAE grade 3/4 (32% and 37%, respectively). Diarrhea was reported by 19% and was CTCAE grade 1/2 in all cases. Peripheral neuropathy newly occurred or worsened in 29% with 24% CTCAE grade 1/2. Other adverse events with CTCAE grade ≥ 3 were atrial fibrillation (2x), liver failure, gastrointestinal bleeding, gastroenteritis, hypocalcemia, syncope, hypotension and post-surgical bleeding. Dose reductions with regard to the PANORAMA trial dosing schedule (San-Miguel JF et al., Lancet Oncol, 2014) were performed either upfront in patients deemed unable to tolerate full doses or during the course of treatment due to adverse events. Nineteen patients (79%) started with full dose PAN; doses were reduced and/or discontinued either upfront or during treatment in 14 patients (58%). In conclusion, FVD showed efficacy in a heavily pretreated MM patient population with a high degree of high risk patients according to cytogenetics and patients refractory to novel agents including PI. With dose reductions in a significant proportion, treatment was tolerated by most patients. However, caution should be exercised especially in elderly patients with restricted general condition where upfront dose reduction seems an appropriate measure to reduce the risk of severe adverse events. Efficacy also in patients refractory to the second generation PI CFZ warrants further investigation of FVD in this difficult to treat patient population. Disclosures Baertsch: Amgen: Other: travel grant; Novartis: Honoraria, Other: travel grant, Research Funding; Janssen: Other: travel grant; BMS: Other: travel grant. Hillengass:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Research Funding; Celgene: Honoraria; BMS: Honoraria. Schönland:Janssen, Prothena, GSK: Consultancy, Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommations, Patents & Royalties, Research Funding, Speakers Bureau. Hegenbart:Janssen: Honoraria, Other: Travel grant; Pfizer: Other: Travel grant. Goldschmidt:Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Raab:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; BMS: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.5686.5686

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Hematological Oncology, Wiley, Vol. 36, No. 1 ( 2018-02), p. 258-261

Abstract: In multiple myeloma (MM), the synergy between immunomodulatory drugs (IMiDs) and monoclonal antibodies (MABs) has been demonstrated in several pivotal trials. However, disease refractory to either class of compounds remains a major therapeutic challenge. We here report on 3 heavily pretreated MM patients who were refractory to pomalidomide as well as to MABs against CD38 (daratumumab) or CD20 (rituximab), respectively, but who responded to retreatment with the same agents in combination. Responses were durable with PFS of 7, 10 (ongoing), and 30 months from initiation of combination treatment. The combination of IMiDs with MABs directed against MM cell surface antigens can overcome refractoriness to both agents.

Type of Medium: Online Resource

ISSN: 0278-0232 , 1099-1069

URL: Issue

URL: Article

DOI: 10.1002/hon.v36.1

DOI: 10.1002/hon.2473

Language: English

Publisher: Wiley

Publication Date: 2018

detail.hit.zdb_id: 2001443-0