ABSTRACT
Background: Second allogeneic hematopoietic cell transplant (sAHCT) might be indicated following a graft failure or disease relapse after the first one;although it might emerge with high rates of morbidities and mortality. Currently, there is a limited number of publications on this matter in the literature, here we aimed to share our sAHCT experience from a single center. Methods: Data from 51 patients who were eligible for sAHCT between 2001 and 2021 was evaluated retrospectively. All data was obtained from the Ankara University Faculty of Medicine, Department of Hematology and Bone Marrow Transplant Unit. Results: 51 patients were included in the present study. Median age at sAHCT was 34 (18- 65) and female/ male ratio 19/ 32 (37.3% / 62.7%). The same donor from the first transplant was eligible for sAHCT for most patients (n= 46, 90.2 %). sAHCT indication was graft failure for 11 patients (21.6 %) whereas 40 (78.4 %) patient went on sAHCT for disease relapse. Patients' diagnoses were as follows: acute myeloid leukemia (n= 26, 50.9 %), acute lymphoblastic leukemia (n=9, 17.6 %), myelodysplastic syndrome (n= 6, 11.8 %), aplastic anemia (n= 6, 11.8 %) and others (CMML, CML, biphenotypic leukemia). Median number of transplanted CD34+ hematopoietic cells was 5.77 x x106/ kg (1.11- 8.29). Stem cell source was either bone marrow (n= 5, 9.8%) or peripheral blood (n= 46, 90.2 %). Myeloablative conditioning regimens were used for most sAHCTs (n= 30, 58.8%). Median overall survival (OS) rates for graft failure and disease relapse groups were 12.8 and 18.7 months, respectively (p= 0.63). During early transplant phase, 20 patients (39.2 %) died due to bone marrow aplasia, transplant failure or other complications. 1 year OS of the entire cohort was 33.3 % whereas 2-y- OS was 21.6% (95% CI= 25-45). 2 patients (3.9 %) died due to COVID19 during transplant process. On univariate analysis, sex, time from the first transplant (<12 months/ ≥12 months), conditioning intensity, sAHCT indication did not statistically significantly influence OS. Multivariate analysis confirmed a lower ECOG score (<2) at sAHCT significantly increased OS (p= 0.001). Conclusions: Based on this single center study, sAHCT is an efficacious treatment modality especially for patients with lower ECOG scores. sAHCT may offer long term survival for both graft failure and disease relapse states.
ABSTRACT
Introduction: Patients with multiple myeloma (MM) have an inherently compromised humoral and cellular immunity predisposing to Covid-19 infection. Factors associated with increased risk of adverse COVID-19 outcome is unclear. The aim of our retrospective analysis was to evaluate COVID-19 infection outcome among our myeloma patients and to define the possible prognostic parameters. Patients And Methods: Between March 2020- February 2022, 10 myeloma patients were diagnosed with COVID infection confirmed by PCR test and computer tomography (CT). The severity of SARS-CoV-2 infection was classified according to WHO definition as: mild: symptomatic without pneumonia or hypoxia;moderate: with or without signs of pneumonia with SpO2 >90% on room air;severe disease: with symptoms of pneumonia and respiratory rate> 30/min, severe respiratory distress or SpO2 <90% on room air. Critical disease: with acute respiratory distress syndrome (ARDS), sepsis and septic shock. In addition, CALL (comorbidity-age-lymphocyte count-lactate dehydrogenase) score was used. All patients were given supportive care including heparin and 0.4 gr/kg/day intravenous immunoglobulin for those presenting with immunoparesis regardless of IgG treshold of 4.0 gr/L. Convalescent or monoclonal plasma was not used. All anti-myeloma treatments were discontinued until full recovery. Results: Baseline characteristics of our patients are summarized in Table 1. The median age at onset of COVID-19 was 62 years. Three patients were therapy naive, two newly diagnosed MM and one with smoldering MM. At the time point of COVID-19 diagnosis, eight patients were being followed without treatment. Twenty patients were followed out-patient without any treatment and with full recovery. Eighteen (16%) patients were admitted to ICU and 13 (12%) required invasive mechanic ventilation. Two patients received hydroxychloroquine, 68 received favipiravir, one patient received anakinra and two patients received tocilizumab. Full recovery from COVID-19 infection with regression of clinic symptoms and achievement of PCR negativity of COVID-19 was observed in 93 (84.5%) patients and 17 (15.5%) patients died due to severe COVID-19 pneumonia with respiratory and multi-organ failure. No death due to thromboembolic event was observed. As expected, high CALL risk score (HR:0.17 (95% CI: 0.06-0.48) and higher COVID severity grade (HR:0.26 (95% CI: 0.07- 0.97) were detrimental. Age did not have an impact. However response <VGPR (HR: 3.1 (95% CI: 1.0-9.6);p=0.04) or immunoparesis (HR: 6.59 (95% CI: 1.44-30.1);p=0.01) were correlated (Kappa CE: 0.212, p=0.03) and associated with worse COVID-19 outcome (Figure 1-2-3). In MVA with age, response, Call score, vaccine, immunoparesis entered in the model only immunoparesis was significant (HR: 6.5, p=0.016). Mortality prior to introduction of vaccines reduced to 3.6 % compared with 11.8 % at the pre-vaccine period. There was a trend to increase in Covid infection incidence recently due to the Omicron variant. Conclusion: Among 110 MM patients, the mortality rate is less than the one reported by IMS during the beginning of the pandemic. In our experience COVID-19 infection severity and mortality decreases with anti-Covid vaccination, response ≥VGPR or lack of immunoparesis. Importantly, MM patients with COVID-19 infection need close monitoring for severe COVID-19-related complications, and correction of humoral immunity may be life-saving. .
ABSTRACT
Introduction: Extramedullary disease (EMD) in patients (pts) with multiple myeloma (MM) is a poor prognostic feature which is not curable with currently approved treatments. Consequently, there is a significant unmet need for effective therapies with good safety profiles. Daratumumab with cyclophosphamide, bortezomib and dexamethasone (daraVCD) is a novel treatment combination with a good efficacy profile in pts with EMD based on preclinical synergistic data. Methods: EMN19 is a phase 2, open-label, multicenter study which aims to enroll 40 MM pts presenting with EMD either at diagnosis or following one line of treatment but not refractory to bortezomib-based regimens, from 8 sites in Turkey, Greece and Italy. Pts with bortezomib or daratumumab hypersensitivity, who received previous autologous stem cell transplant (ASCT) ≤12 weeks before Day 1 of treatment Cycle 1, or with previous allogenic stem cell transplant were excluded. Daratumumab was initially administered intravenously at 16 mg/mL, and since July 2020 has been administered subcutaneously at a fixed dose of 1800 mg, weekly during Cycles 1-2, every 2 weeks for Cycles 3-6, and every 4 weeks thereafter. Intravenous bortezomib 1.5 mg/m 2 and oral/intravenous cyclophosphamide 300 mg/m 2 is administered weekly, and oral/intravenous dexamethasone 20 mg is administered on Days 1, 2, 8, 9, 15, 16, 22 and 23. DaraVCD will be administered until progression or unacceptable toxicity unless refractory disease is detected by the end of Cycle 3 (progressive disease [PD] or failure to achieve a confirmed partial response [PR] or better). The present analysis includes pts who initiated study treatment ≥3 months prior to the cut-off date (01 June 2021). Results: In total, 34 patients were screened, 27 patients were enrolled, 2 relapsing patients died during the screening phase due to severe COVID-19 infection, 22 pts were analyzed (59% female;median age 56 years, range 44-77);14 pts (64%) were still on treatment and 8 (36%) discontinued;due to inadequate response after 3 cycles of treatment (n=3, 38%), PD (n=4, 50%), death (n=1, 13%). Fourteen pts (64%) were newly diagnosed and 8 (36%) first relapsed. International Staging System stage at baseline was I, II and III for 8 (36%), 9 (41%) and 5 (23%) pts, respectively. Eastern Cooperative Oncology Group performance status was 0, 1 and 2 for 14 (64%), 7 (32%), and 1 patient (5%), respectively. On average, 3.0 (range 1-20) extramedullary plasmacytomas were observed per patient;most commonly reported sites were thorax (6 pts, 27%), brain, head and lower extremities (4 pts, 18% each). Twenty (91%) pts had ≥1 serious or non-serious treatment-emergent adverse event (TEAE);8 pts (36.4%) experienced ≥1 sTEAEs;COVID-19 infection (n=3, 14%) urinary tract infection (n=2, 9%), infectious myocarditis, hip arthroplasty, pneumonia, cytomegaloviral pneumonia and thrombocytopenia (n=1 each, 4.5%). Thirteen (59%) pts ≥1 Grade 3/4 TEAE;neutropenia observed in 8 pts (36%), followed by thrombocytopenia (n=4, 18%) and COVID-19 infection (n=3, 14%). Overall, 16 (73%) pts missed ≥1 dose of any of the study drugs;2 (9%) pts missed ≥1 dose due to COVID-19 infection (7 doses), 8 (36%) due to COVID-19 vaccination (37 doses), 2 (9%) due to other COVID-19-related issues (65 doses), 10 (46%) due to other safety events (104 doses) and 9 (41%) due to other reasons (25 doses). Overall, 20 cycle delays were observed in 13 (59%) pts, with median (range) delay of 12.0 (4-133) days. Two pts (9%) had a cycle delay due to COVID-19 infection (2 cycles), 1 (5%) due to COVID-19 vaccination (1 cycle), 5 (23%) due to adverse events (8 cycles), 2 (9%) due to ASCT (2 cycles) and 7 (32%) due to other reasons (7 cycles). Total number of missed doses (missed doses due to COVID-19-related issues) were 17 (3) for daratumumab, 53 (11) for bortezomib, 45 (9) for cyclophosphamide and 123 (86) for dexamethasone;238 doses missed in total. No fatalities occurred due to any infection. Conclusions: DaraVCD was associated with a good safety profile in this high ri k MM with EMD patient population. The COVID-19 impact on missed doses was greater for dexamethasone (>60% of missed doses) than other components (~20%), however overall, the pandemic did not significantly affect the patients' safety and data integrity of the study. The enrollment in the study is ongoing, and more safety and efficacy data will become available with the inclusion of additional pts in an updated analysis. Disclosures: Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau. Tuglular: GSK: Honoraria, Research Funding;Amgen: Honoraria, Research Funding;Karyopharm: Honoraria, Research Funding;Abbvie: Honoraria, Research Funding;Janssen-Cilag: Honoraria, Research Funding;Genesis Pharma: Honoraria, Research Funding;Sanofi: Honoraria, Research Funding. Cavo: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;GlaxoSmithKline: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Adaptive Biotechnologies: Consultancy, Honoraria. Gay: GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Membership on an entity's Board of Directors or advisory committees;Bluebird bio: Membership on an entity's Board of Directors or advisory committees. Katodritou: GSK, Amgen, Karyopharm, Abbvie, Janssen-Cilag, Genesis Pharma, Sanofi: Honoraria, Research Funding. Merante: EMN Italy Medical Monitor: Research Funding. Manousou: Health Data Specialists: Current Employment. Sonneveld: Karyopharm: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Celgene/BMS: Consultancy, Honoraria, Research Funding;SkylineDx: Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding. Terpos: GSK: Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Genesis: Consultancy, Honoraria, Research Funding;Novartis: Honoraria;Janssen-Cilag: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;BMS: Honoraria;Takeda: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding.
ABSTRACT
Introduction: Maintenance with lenalidomide after high dose melphalan consolidation is known to extend progression free survival (PFS) in multiple myeloma (MM) patients [1]. Lenalidomide may induce neutropenia and lymphopenia, exposing patients to infections. On the other hand, there have been small case series and brief reports suggesting IMIDs might protect from severe Covid-19 [2] [3]. Here, we resumed our set of MM patients who were diagnosed with Covid-19 infection and compared outcomes based on continuous lenalidomide maintenance. Patients and Methods: 45 MM patients were diagnosed with Covid- 19 in our department between March 2010- December 2020. Here we will be reporting the data of those on lenalidomide (n= 14) and not receiving Lenalidomide maintenance(n:15). Results were compared on Lenalidomide but no Covid-19 (Table 1). All statistical analyses were performed via SPSS statistics version 20.0 software. Results: Table 1 summarizes patient demographics and essential laboratory data: Infection fatality rate for lenalidomide maintenance and no lenalidomide groups were 27.5 % and 33.3 %, relatively. Recovery rates were 71.5 % and 66.7 %, relatively. Both these results were in favor of lenalidomide maintenance. Conclusion: Although cytopenias and immunoparesis may develop during continuous maintenance, lenalidomide seems to be safe and has effects in favor of less severe Covid-19 forms and mortality among MM patients. Based on our experience we do not recommend discontinuation during the pandemic.