- |||||||||| Empliciti (elotuzumab) / AbbVie, BMS
A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Myelofibrosis (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5326; P2 These findings led to the clinical development of PRM-151 (recombinant human pentraxin-2) as an anti-fibrotic agent for patients with myelofibrosis (MF) (Verstovsek, EHA 2019)...Finally, elotuzumab, a SLAMF7-targeting monoclonal antibody, inhibited the differentiation of MF patient-derived fibrocytes in vitro and romiplostim-induced MF and splenomegaly in vivo...Elotuzumab is dosed intravenously weekly at 10 mg/kg per dose for the first 8 doses, followed by 20 mg/kg every 4 weeks, per the label for its use in multiple myeloma in combination with pomalidomide and dexamethasone...Current status: The study (clinicaltrials.gov identifier: NCT04517851) is ongoing; 2 participants have been enrolled and treated thus far. Updated enrollment information will be provided.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Venetoclax-Ponatinib for T315I/Compound-Mutated Ph+Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5076; The outcome of Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) have greatly improved in tyrosine kinase inhibitors (TKIs) era and is just moving to a chemo-free era using dasatinib and blinatumomab (Foà R, N Engl J Med...Moreover, venetoclax had a strong synergistic effect with ponatinib and dexamethasone on inducing apoptosis of primary blast cells and BaF3 cells expressing p190 BCR/ABL with T315I-mutation in vitro , with a combination index of 0.019 when the suppressing rate is 0.05, while the effect was significant decreased when ponatinib was replaced by dasatinib (Figure 1D-F), a prominent change of mitochondrial membrane potential as well as the cleavage of PARP were also observed in triple-combination treatment group (Figure 1G-H)...A clinical trial also using similar VPD regimen for treatment of R/R Ph+ ALL is ongoing now (Short NJ, Am J Hematol . 2021).
- |||||||||| Arranon (nelarabine) / Novartis
Impact of Nelarabine, Intensive L-Asparaginase, and Protracted Intrathecal Therapy on Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group and the Japan Adult Leukemia Study Group (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5074; Good or poor PSL responses were defined as <1.0 × 10 9 /L or ≥1.0 × 10 9 /L blasts in peripheral blood at day 8 following a 7-day PSL pre-phase plus one IT dose of methotrexate, respectively...ALL-T11 was characterized by dexamethasone in IA, the additional use of E. coli derived L-asp (5000 U/m 2 × 8 in IB, 10,000 U/m 2 × 4 in reinduction protocol IIB for SR and HR groups, and 12,500 U/m 2 × 4 in protocol M for SR), incorporation of NEL (5-day course of 650 mg/m 2 /day) in HR or VHR groups (6 or 1–2 courses, respectively), and elimination of prophylactic cranial radiotherapy (CRT)... The addition of NEL, intensified L-asp, and protracted IT in AIEOP-BFM-ALL 2000 based treatment showed encouraging outcomes with acceptable toxicities despite the limited use of CRT and HSCT.
- |||||||||| Defitelio (defibrotide) / IRCCS San Raffaele Hospital, Jazz
Defibrotide Therapy for Sars CoV2 Acute Respiratory Distress Syndrome (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4908; Outcomes were promising, including an overall survival of 75% in a patient population with a historically high mortality rate. ( The study was supported by a research grant from Jazz Pharmaceuticals )
- |||||||||| Nplate (romiplostim) / Amgen, Kyowa Kirin
Immunomodulation with Romiplostim in Young Adult Primary Immune Thrombocytopenia (ITP) As Second-Line Strategy (iROM-study) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4816; Rituximab and dexamethasone have the potential to induce tolerogenic mechanisms, however with moderate long-term results (12 months), median age 31.5 years (IQR 8.75), with a median platelet count at enrollment of 26x10 9 /l (IQR 41) and 49.5x10 9 /l (IQR 88.5), and at week 52, 168x10 9 /l (IQR 88) and 96x10 9 /l (IQR 23.5), respectively. All patients were on ITP treatment at enrollment (steroids and/or IVIG).
- |||||||||| dexamethasone / Generic mfg.
Neutrophil Metabolic Rewiring in Severe and Mild COVID-19 (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4793; Broad inhibition of hyperinflammation by dexamethasone is a mainstay of severe COVID-19 treatment...Isotope tracing experiments were carried out to understand how nutrients were utilized in neutrophils in context of inflammation. We will describe mechanistic work testing whether metabolic features we observe in severe COVID-19 patients regulate the inflammatory response of human neutrophils.
- |||||||||| dexamethasone / Generic mfg.
COVID-19 Infection and Outcomes at a Comprehensive Sickle Cell Center (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4768; By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ + thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis.
- |||||||||| dexamethasone / Generic mfg.
Bleeding Risk in Patients with Multiple Myeloma Treated for Venous Thromboembolism (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4681; Anticoagulant agent of choice was warfarin in 45.7% (734), low-molecular weight heparin (LMWH) in 29% (466), and direct oral anticoagulants (DOAC) in 25.3% (405). There were no significant differences in age/sex distribution, comorbidity burden, history of significant bleeding, or use of IMiD across the different types of anticoagulation (Table 1).
- |||||||||| Favorable Outcomes with Thiotepa/Busulfan-Based Conditioning and Autotransplant for Patients with Aggressive B-Cell Lymphoma and Secondary CNS Involvement (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4562;
HDT conditioning regimens were thiotepa, busulfan, melphalan, rituximab (TBMR, n=52, 91%) or thiotepa, busulfan, cyclophosphamide (TBC, n=5, 9%)...Conclusion : In one of the largest studies of this conditioning regimen in SCNSL to date, we found that high-dose thiotepa/busulfan-based conditioning with ASCT is associated with favorable outcomes for patients with aggressive B-cell lymphoma and secondary CNS involvement, with 4-year OS ~75% in this study. Although SCNSL has been historically associated with a poor prognosis, an increasing proportion of patients may achieve long-term survival after intensive therapy with HD-MTX-based induction and thiotepa/busulfan-based HDT and ASCT.
- |||||||||| dexamethasone / Generic mfg., lenalidomide / Generic mfg., carfilzomib / Generic mfg.
Phenotypic High-Risk Disease in the Context of Carfilzomib and Lenalidomide Combination Induction Therapy for Newly Diagnosed Transplant-Eligible Myeloma Patients (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4557; Methods The UK NCRI Myeloma XI trial is a phase III randomised controlled trial that recruited 2568 newly diagnosed transplant eligible patients, of which 526 were randomised to receive the induction combination KRdc comprising carfilzomib (K, 36mg/m2 IV d1-2, 8-9,15-16 (20mg/m2 #1d1-2)), lenalidomide (R, 25mg PO d1-21), dexamethasone (d, 40mg PO d1-4,8-9,15-16) and cyclophosphamide (c, 500mg PO d1,8) as part of an adaptive trial design...401/526 (76%) of patients underwent high dose melphalan and ASCT on trial after KRdc induction...Discussion The combination of a second-generation immunomodulatory agent and proteasome inhibitor in the KRdc induction regimen is associated with deep responses and only a very small proportion of patients have primary refractory disease. Early relapse after KRdc and ASCT occurred in 9% of patients and was associated with high bone marrow disease burden and molecular high-risk features.
- |||||||||| CLBR001 + SWI019 / AbbVie
First in Human Study of an on/Off Switchable CAR-T Cell Platform Targeting CD19 for B Cell Malignancies (CLBR001 + SWI019) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4467; P1 Following cyclophosphamide and fludarabine lymphodepletion, patients receive a single dose of CLBR001 cells, followed by daily infusion of SWI019 for 7 days...This event subsided within 24 hours of administration of dexamethasone with no recurrence of CRS observed with continued administration of a reduced dose (50%) of SWI109, providing support for the tunability of the platform...Accrual is ongoing in dose expansion cohorts of both CLBR001 cells and SWI019 switch. Updated results will be presented at the meeting.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Kineret (anakinra) / SOBI
Anakinra Targeting Cytokine Release Syndrome Associated with Chimeric Antigen Receptor T-Cell Therapies (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4457; CRS events in cilta-cel-treated patients in CARTITUDE-1 were common, generally low-grade, and successfully managed with standard tocilizumab +/- dexamethasone. The use of anakinra should be considered in patients with persistent CRS/inflammatory symptoms despite tocilizumab use, and in particular in patients with HLH/MAS-like symptoms/phenotype occurring following CRS or in the absence of prior CRS.
- |||||||||| Darzalex IV (daratumumab) / J&J
A Phase 2 Study of Extended Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4401; Importantly, the rate and depth of MRD-negativity improve beyond cycle 8, suggesting that extended Dara-KRd without ASCT may generate rates of sCR and MRD-negativity comparable to KRd with ASCT. Yearly longitudinal determinations of MRD after completion of 24 cycles of Dara-KRD protocol treatment will generate information on the durability of MRD and the role of ASCT compared to shorter treatments with Dara-KRd, with and without ASCT.
- |||||||||| Xpovio (selinexor) / Karyopharm
Selinexor-Based Regimens in Patients with Multiple Myeloma after Prior Anti-B-Cell Maturation Antigen Treatment (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4393; P1b/2 Results In total, 11 pts with prior anti-BCMA therapy (6 pts with belantamab mafodotin; 1 each with MEDI2228, SEA-BCMA, BCMA BITE; 2 with idecabtagene vicleucel) were treated with 5 X-containing regimens (Table 1): 9 pts were treated with triplets XPd (4), XVd (3), or XKd (2) and 2 pts with quadruplets XPVd (1) or XPEd (1)...Conclusions In this follow-up cohort of heavily pretreated pts, a majority of whom with MM refractory to ADC-BCMA, we demonstrate impressive potency and durability of the X-based treatments, particularly as compared to that of their prior anti-BCMA therapies. These data support the rationale for the development of novel regimens containing X plus immunomodulatory drugs or proteasome inhibitors in earlier lines of therapy, including first relapse, and further suggest their strong value in the emerging BCMA RRMM space.
- |||||||||| Darzalex IV (daratumumab) / J&J, Xpovio (selinexor) / Karyopharm
Once Weekly Oral Selinexor, Pomalidomide, and Dexamethasone in Relapsed Refractory Multiple Myeloma (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4390; The all-oral combination of XPd is highly active with an ORR of 65% at XPd-60, the RP2D, and an ORR of 42% at XPd-40 dose level (compared to expected ORR ~30% for Pd). The high ORR that was achieved at the RP2D, including in patients previously treated with anti-CD38 mAb, supports XPd-60 as a promising therapy with no significant cross-resistance to anti-CD38, PIs or lenalidomide.
- |||||||||| Sarclisa (isatuximab-irfc) / Sanofi
A Multi-Center, Phase 1b Study to Assess the Safety, Pharmacokinetics and Efficacy of Subcutaneous Isatuximab Plus Pomalidomide and Dexamethasone, in Patients with Relapsed/Refractory Multiple Myeloma (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4386; As of March 31, 2021, 7 pts (58%) IV, 4 pts (33%) SC1000, and 7 pts (70%) SC1400 remained on study treatment. Median time from initial MM diagnosis to first study treatment was ~5 years, and the median (range) number of prior lines of therapy was: 3.5 (2-7) in IV, 3.0 (2-6) in SC1000, and 2.5 (1-4) in SC1400 pts.
- |||||||||| Melflufen (melphalan flufenamide) / Oncopeptides
OCEAN (OP-103): Melflufen/Dexamethasone Compared with Pomalidomide/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma—Age Subgroup Analysis of Older Patients (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4383; P2, P3 Median PFS was 4.4 mo vs 4.9 mo in age <65 y, 7.2 mo vs 4.9 mo in age 65-74 y, and 9.3 mo vs 4.9 mo in age ≥75 y, with melflufen vs pom, respectively, with significant differences in the 65-74 y and ≥75 y groups ( Table ). In pts who had not received prior ASCT, median PFS was 10.8 mo vs 4.7 mo in age <65 y (HR, 0.83 [95% CI, 0.43-1.58]; P =0.57), 9.3 mo vs 3.9 mo in age 65-74 y (HR, 0.57 [95% CI, 0.38-0.86]; P <0.01), and 9.3 mo vs 4.9 mo in age ≥75 y (HR, 0.44 [95% CI, 0.24-0.80]; P <0.01), with melfluflen vs pom, respectively.
- |||||||||| SEA-BCMA / Seagen
SEA-BCMA, an Investigational Nonfucosylated Monoclonal Antibody: Ongoing Results of a Phase 1 Study in Patients with Relapsed/Refractory Multiple Myeloma (SGNBCMA-001) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4382; P1 Parts B and C aim to optimize efficacy by testing intensified dosing (Part B; weekly [Q1W] induction dosing of SEA BCMA for 8 weeks is followed by Q2W maintenance dosing) and dexamethasone (DEX) combination therapy (Part C) in pts who have received ≥3 prior lines of therapy for MM and are triple‑class refractory...Following a safety monitoring review, premedication with acetaminophen + antihistamine was introduced to mitigate IRRs in expansion cohorts...Expansion cohorts testing intensified SEA-BCMA dosing and the addition of DEX are underway to further assess the safety, tolerability, and estimate of SEA-BCMA activity in the context of these treatment approaches. An additional expansion cohort (Part D), testing the combination of SEA-BCMA with pomalidomide and DEX in pts who have received ≥2 prior lines of therapy, is now enrolling.
- |||||||||| mezigdomide (CC-92480) / BMS
CC-92480, a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD) Agent, in Combination with Dexamethasone (DEX) and Bortezomib (BORT) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Phase 1/2 Study CC-92480-MM-002 (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4373; P1/2 Introduction : CC-92480 is a potent, novel CELMoD ® compound designed for rapid and maximal degradation of Ikaros and Aiolos, that has shown immunostimulatory effects and enhanced tumoricidal activity in myeloma cells, including those resistant to lenalidomide (LEN) and pomalidomide (POM)...Prior therapies included stem cell transplantation (57.9%), BORT (78.9%), carfilzomib (CFZ, 21.1%), LEN (100%), POM (47.4%), and anti-CD38 mAbs (36.8%); 21.1% of the pts had extramedullary disease and 21.1% were triple-class refractory (refractory to immunomodulatory drug, PI, and anti-CD38 mAb)...In the CC-92480-MM-002 study, a CC-92480 + BORT + DEX expansion cohort is ongoing at the RP2D, as well as a CC-92480 + CFZ + DEX cohort. Updated data will be presented at the meeting.
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