Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

BACKGROUND: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. METHODS: Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. RESULTS: Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. CONCLUSION: Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP).

INTRODUCTION: Belantamab mafodotin (BM) is a new anti-BCMA antibody-drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). METHODS: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Thirty-three patients were included with a median of 70 years of age (range, 46-79 years). Median time from diagnosis was 71 months (range, 10-858 months). Median prior lines was 5 (range, 3-8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1-16 doses), with a median follow-up of 11 months (6-15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92-5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10-0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107-740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). CONCLUSIONS: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Characteristics and Outcomes of Adult Patients in the PETHEMA Registry with Relapsed or Refractory FLT3-ITD Mutation-Positive Acute Myeloid Leukemia.

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.

Impact of the subcutaneous formulations of trastuzumab and rituximab on efficiency and resource optimization in Spanish hospitals: H-Excelencia study.

BACKGROUND: Subcutaneous (SC) versus intravenous (IV) administration is advantageous in terms of patient convenience and hospital efficiency. This study aimed to compare the effect of optimizing the processes involved in SC versus IV administration of rituximab and trastuzumab on hospital capacity and service quality. METHODS: This cross-sectional resource utilization study interviewed oncologists, hematologists, nurses, and pharmacists from 10 hospitals in Spain to estimate changes in processes associated with conversion from IV to SC rituximab and trastuzumab, based on clinical experience and healthcare use from administrative databases. RESULTS: Efficient use of SC formulations increased the monthly capacity for parenteral administration by 3.35% (potentially increasable by 5.75% with maximum possible conversion according to the product label). The weekly capacity for hospital pharmacy treatment preparation increased by 7.13% due to conversion to SC formulation and by 9.33% due to transferring SC preparation to the cancer treatment unit (potentially increasable by 12.16 and 14.10%, respectively). Monthly hospital time decreased by 33% with trastuzumab and 47% with rituximab. In a hypothetical hospital, in which all processes for efficient use of SC rituximab and/or trastuzumab were implemented and all eligible patients received SC formulations, the estimated monthly capacity for preparation and administration increased by 23.1% and estimated hospital times were reduced by 60-66%. CONCLUSIONS: Conversion of trastuzumab and rituximab to SC administration could improve the efficiency of hospitals and optimize internal resource management processes, potentially increasing care capacity and improving the quality of care by reducing time spent by patients at hospitals.

Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.

BACKGROUND: Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. METHODS: In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. RESULTS: Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60-79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17-10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). CONCLUSIONS: In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Efficacy, safety and quality-of-life associated with lenalidomide plus dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience.

Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849).

Lenalidomide is effective as salvage therapy in refractory or relapsed multiple myeloma: analysis of the Spanish Compassionate Use Registry in advanced patients.

We evaluated the clinical results of lenalidomide (Len) as a compassionate salvage therapy in refractory/relapsed multiple myeloma (MM) patients. A nationwide multi-centre, retrospective research study was performed to evaluate clinical data from patients with advanced MM for which compassionate use of lenalidomide was requested. The primary endpoints were the overall response rate (ORR) and the time to progression (TTP). Secondary objectives included safety and overall survival (OS) since starting of lenalidomide therapy. Data collected from the Spanish Compassionate Use Registry included 111 patients treated in 2006-2008. The median (range) number of previous treatment lines was 3 (1-8). The median duration of lenalidomide treatment while on study was of 4.9 months (1-18). Dexamethasone was given concomitantly with Len in 89% of patients. The ORR was 66% (4% of patients had stringent complete, 11% complete and 11% very good partial responses). Median TTP and OS were 13.0 and 17.4 months, respectively. The depth of response was significantly associated with a longer OS. Toxicity, mainly myelosuppression, was predictable and manageable with Len dose adjustments and cytokine support. Lenalidomide as salvage compassionate therapy in refractory/relapsed MM showed, in this series of heavily pre-treated patients, similar efficacy to that reported in pivotal clinical trials with acceptable tolerance.

Different patterns of relapse after autologous peripheral blood stem cell transplantation in multiple myeloma: clinical results of 280 cases from the Spanish Registry.

BACKGROUND AND OBJECTIVES: Autologous peripheral blood stem cell (PBSC) transplantation is widely used to treat patients with multiple myeloma (MM). However, only a small fraction of patients remain free of disease in the long-term and most patients will finally relapse. The clinical presentation of relapse after transplantation is very heterogeneous and few reports have analyzed this situation. We report the clinical patterns of relapses after autologous transplantation of 280 patients with MM included in a Spanish Multicenter Registry. DESIGN AND METHODS: The medical records of 560 patients with MM transplanted in different centers in Spain, included in the Spanish Registry of Transplant in Multiple Myeloma, were reviewed. At diagnosis, 48 (8%) had stage I disease, 143 (25%) stage II and 369 (65%) stage III. The median time from diagnosis to transplantation was 13 months (4-143). The median age was 53 years (23-70). Of the 502 patients assessable for response to intensification therapy after transplantation, 241 (48%) achieved a complete response and 220 (43%) a partial response. The clinical characteristics of 280 patients (52%) who had relapsed after transplantation were retrospectively assessed during long-term post-transplantation follow-up. RESULTS: At a median follow-up of 23 months, 280(52%) patients had relapsed or progressed after transplantation. The median overall survival was 52 months (SE 8), (CI 95% 37-68) and median estimated progression-free survival was 33 months (SE 2.2, CI 95% 27-38). The median period for relapse was 30 months (2-84) with an actuarial risk of progression or relapse at 60 months after transplantation of 78%. The clinical patterns of relapse were very heterogeneous: 40 cases (14%) presented extramedullary manifestations with multiple plasmacytomas as the main symptoms of relapse, with a minimum or null monoclonal component (MC). In 51 cases (18%) only an insidious increase of MC protein in serum or urine was detected without other clinical manifestations. In 6 cases (2%) the relapse had criteria of plasmacytic leukemia. The remaining patients presented progressive increase of MC associated with plasmacytic bone marrow infiltration and different clinical myeloma symptoms, mainly new osteolytic lesions. The therapeutic approach was also very heterogeneous, with a global antitumoral response of 30%. Median overall survival after relapse was 14 months (SE 1.4) (CI 95% 11-17). INTERPRETATION AND CONCLUSIONS: The patterns of relapse of MM after high-dose therapy are very heterogeneous. The different clinical expressions of relapse may be due to clonal selection after high-dose therapy and could indicate the persistence of a resistant clone. Some patients relapse with extraosseous plasmacytomas without systemic disease. These findings suggest the need for an individualized approach during clinical follow-up after transplantation. Regarding treatment response, patients with myeloma who relapse after high-dose chemotherapy have been classically considered to have few therapeutic options. However, we observed that after different lines of treatment, at least one-third of patients responded, with a median overall survival, after relapse of 14 months. New drugs, such as thalidomide, have been recently proved to be effective in MM patients and could increase the response rate and survival of these patients.

Trasplante de células progenitoras hematopoyéticas como tratamiento de rescate en pacientes con linfomas no hodgkinianos agresivos / Hematopoietic stem cell transplantation as salvage treatment in patients with aggresive non-Hodgkin's lymphoma

Fundamento: La realización precoz del trasplante de células progenitoras hematopoyéticas (TPH) en pacientes con linfomas no hodgkinianos (LNH) agresivos es una indicación controvertida. Métodos: Análisis retrospectivo de 86 pacientes con LNH agresivos tratados con quimioterapia MACOP/VACOP-B. El TPH se utilizó como tratamiento de rescate en pacientes con edad inferior o igual a 65 años con progresión o recaída quimiosensible. Se determinaron las supervivencias libre de progresión (SLP) y global (SG) con el método de Kaplan-Meier. Se compararon los porcentajes de respuesta y las funciones de supervivencia entre los grupos del Índice Pronóstico Internacional (IPI) mediante las pruebas *2 y log-rank, respectivamente Resultados: La mediana de edad de los pacientes fue de 48 años. El 22 por ciento tenían LNH-T y el 57 por ciento tenían IPI de intermedio-alto y alto riesgo. Hubo 6 muertes por toxicidad (7 por ciento), y 42 (48,8 por ciento) pacientes fracasaron al tratamiento de primera línea. De ellos, 31 fueron candidatos a TPH por edad inferior o igual a 65 años, aunque finalmente se trasplantaron 21 (incluyendo 13 de mayor riesgo). Se observó una asociación estadísticamente significativa entre la SLP y el IPI: 61,9 por ciento para los grupos bajo y bajo-intermedio (menor riesgo) frente al 28,2 por ciento para los de mayor riesgo (p = 0,0007). Con una mediana de seguimiento de 4,8 años, la SG fue del 80,5 por ciento para los grupos de menor riesgo frente al 52,6 por ciento (p = 0,01) para los de mayor riesgo, y del 83,7 por ciento frente al 62,0 por ciento (p = 0,02) para los mismos grupos en pacientes con edad inferior o igual a 65 años. La mediana de seguimiento posfracaso del tratamiento quimioterápico fue de 42,7 meses. Conclusiones: En este análisis retrospectivo la SG de los pacientes con LNH agresivos utilizando el TPH como tratamiento de rescate es similar a la comunicada utilizando el TPH más precozmente. (AU)