Showing papers by "Mario Boccadoro published in 2023"

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

Abstract: In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6-12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network.

Abstract: T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T cells (CAR T cells) have revolutionised multiple myeloma therapy, but adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, hypogammaglobulinaemia, and infections are common. This Policy Review presents a consensus from the European Myeloma Network on the prevention and management of these adverse events. Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome. Other anti-IL-6 drugs, high-dose corticosteroids, and anakinra might be considered in refractory cases. ICANS often arises concomitantly with cytokine release syndrome. Glucocorticosteroids in increasing doses are recommended if needed, as well as anakinra if the response is inadequate, and anticonvulsants if convulsions occur. Preventive measures against infections include antiviral and antibacterial drugs and administration of immunoglobulins. Treatment of infections and other complications is also addressed. T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T cells (CAR T cells) have revolutionised multiple myeloma therapy, but adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, hypogammaglobulinaemia, and infections are common. This Policy Review presents a consensus from the European Myeloma Network on the prevention and management of these adverse events. Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome. Other anti-IL-6 drugs, high-dose corticosteroids, and anakinra might be considered in refractory cases. ICANS often arises concomitantly with cytokine release syndrome. Glucocorticosteroids in increasing doses are recommended if needed, as well as anakinra if the response is inadequate, and anticonvulsants if convulsions occur. Preventive measures against infections include antiviral and antibacterial drugs and administration of immunoglobulins. Treatment of infections and other complications is also addressed.

B03 carfilzomib and lenalidomide for primary plasma cell leukemia: final results of the prospective phase 2 emn12/hovon-129 study for patients aged ≥66 years

Abstract: Introduction: Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with poor prognosis. The EMN12/ HOVON-129 study assessed carfilzomib and lenalidomide as first-line therapy in pPCL. Pts ≥18 years were enrolled, with different treatment for those 18-65 and ≥66 years. Here we report the results for pts ≥66 years. Methods: Inclusion criteria were newly diagnosed pPCL (>2x109/L circulating monoclonal plasma cells and/or plasmacytosis >20% of the differential white cell count) and WHO performance status 0-3. Main exclusion criteria were severe cardiac or pulmonary dysfunction and creatinine clearance <15 ml/min. There were no restrictions based on blood counts. Pts ≥66 years received eight 28-day induction cycles of carfilzomib-lenalidomide-dexamethasone (KRd; K: 20/36 mg/m2 days 1,2,8,9,15,16; R: 25 mg days 1-21; d: 20 mg days 1,2,8,9,15,16,22,23), followed by maintenance with KR (K: 27 mg/m2 days 1,2,15,16 for the first 12 cycles; then 56 mg/m2 days 1,15; R: 10 mg days 1-21/28 days) until progression. The primary endpoint was progression-free survival (PFS); secondary endpoints were response rate, overall survival (OS), and toxicity. Results: From Oct 2015 to Aug 2021, we enrolled 61 pts with pPCL: 36 were ≤65 years and 25 ≥66 years. Among pts ≥66 years, median age was 71 years (range 66-84); 68% had bone disease; WHO performance status was 2 in 24% and 3 in 16% of pts. Median plasma cell percentage in bone marrow biopsy was 80% (10-100). Median peripheral blood plasma cell count was 3.8x109/L (range 2.0-52); median platelet count was 142x109/L (range 13-384); median GFR was 56 ml/min (range 24-95). Most of pts had high-risk disease features: 52% had elevated LDH; 20% del(17p), 4% t(4;14), 4% t(14;16), and 48% gain/amp(1q); 12% of pts had extramedullary plasmacytomas; 68% had ISS III and 40% Revised ISS III. At the data cut-off (July 1, 2022), among the 25 pts, 17 (68%) received the planned 8 cycles of induction treatment, achieving ≥ PR in 80%, ≥VGPR in 68%, and ≥CR in 32%; 16 pts (64%) received maintenance treatment. Best response on protocol was ≥PR in 80%, ≥VGPR in 68% and ≥CR in 36%; 3 out of 4 pts in CR who could be evaluated for minimal residual disease (MRD) achieved MRD negativity (10-5) by flow cytometry. With a median follow-up of 24.6 months (range 7.9-59.6), median PFS was 13.8 months (95% CI 9.2-35.5); median OS was 24.8 months (95% CI 14-NR - 16 deaths: 8 disease progression, 2 unknown, 1 pneumonia, 1 sepsis, 1 systemic aspergillus infection, 1 small intestinal SPM, 1 disseminated intravascular coagulation, 1 respiratory failure due to COPD exacerbation). Toxicity rate was 36% both for G3 and for G4 events. G3 and G4 hematologic toxicity rates were 8% and 12%. Infections (20% and 16%) and respiratory events (16% and 4%) were the most common G3 and G4 non-hematologic toxicities. Twenty-two pts (88%) discontinued treatment, mainly because of progression (13 pts, 59%). Conclusions: KRd is a potent strategy to control pPCL in pts ≥66, with not negligible, but generally manageable, treatment-related toxicities. Besides a significant PFS improvement, median OS substantially doubled compared to what has been reported in recent retrospective studies (see the only other prospective trial with Rd) in transplant ineligible, elderly pts with pPCL (Musto P et al. Leukemia. 2014).