Prescription Patterns of Daratumumab in Patients with Multiple Myeloma in Underprivileged Circumstances: A Multicenter Experience in Mexico.

BACKGROUND: Despite novel therapies, multiple myeloma (MM) remains an incurable malignancy, daratumumab (DARA) being a major game changer, may be a good option for treatment. AIMED OF THE STUDY: To assess the prescription patterns of DARA in patients with MM in Mexico. METHODS: 47 patients with MM were analyzed in 13 different hospitals in Mexico. RESULTS: Five (10.5%) of patients received DARA as first line therapy, 13 (27.5%) as second line, whereas 29 (62%) received its in ≥3rd line. In 32% DARA was used in combination with dexamethasone, 64% received DARA on a triple combination, and 4% as a 4 drug combination. Eighty three percent of patients had a response, including 32% in complete remission. Progression free survival (PFS) was higher in patients in ISS stage 1, and in patients achieving ≥PR. Overall survival (OS) was lower in patients not achieving ≥PR, in patients having increased LDH, and extramedullary disease. Grade 1-2 infusion related reactions were present in 34%, and grade 3-4 neutropenia and lymphopenia in 25 and 17% of the patients. CONCLUSIONS: In Mexico, 62% of patients with MM received DARA as a third or further line of treatment. DARA employed as a doublet or triplet combination is useful in relapsed/refractory patients with tolerable adverse events.

Mieloma múltiple en tiempos de SARS-CoV-2 (COVID-19) en México / Multiple myeloma in times of SARS-CoV-2 in Mexico

Resumen El mieloma múltiple (MM) es una enfermedad oncológica heterogénea en su componente molecular que a su vez genera una variabilidad clínica. Su riesgo se define de acuerdo con el Sistema Internacional de Estatificación Revisado, que considera: niveles serios altos de deshidrogenasa láctica y Beta2 microglobulina, niveles bajos de albúmina y la presencia de alguna alteración citogenética, del 17p13, t(14;14), y t(14;16); el grupo de alto riesgo se caracteriza por una recaída temprana y supervivencia corta. En este momento de pandemia por enfermedad por coronavirus 2019 (COVID-19), el manejo de los pacientes con MM se ha afectado indirectamente por la falta de oportunidad en el diagnóstico y el manejo; además de existir datos que sugieren que el estado de inmunosupresión propio de la enfermedad aunado a la terapia inmunosupresora e inmunomoduladora los hace de alto riesgo de complicarse y fallecer cuando adquieren la COVID-19. Sin embargo, no existen registros propios de mieloma que lo corroboren y en los registros de COVID-19/cáncer las complicaciones se reportan principalmente en cáncer de pulmón y los que están dentro de las cuatro semanas de haber recibido quimioterapia intensa. En México y Latinoamérica en una encuesta breve solo se encontraron casos aislados, pero aún falta analizar los datos. La baja frecuencia de pacientes con MM y COVID-19 probablemente esté dada por los cuidados y aislamiento que de antemano se tiene con ellos. Dado que el MM es una enfermedad heterogénea, debemos seguir evaluando el riesgo al diagnóstico y dar el tratamiento pleno a los de alto riesgo. Para ello debemos ajustar las medidas para reducir el riesgo de exposición a la COVID-19, reducir en la medida de lo posible las visitas a las unidades de atención, ajustar los tratamientos de primera línea de acuerdo con las características propias de cada paciente y monitorizar con pruebas para COVID-19 a los pacientes con terapias intensas y aquellos que requieren de trasplante de células progenitoras hematopoyéticas. La pandemia por COVID-19 es una catástrofe sin presente, no solo por la morbimortalidad propia de la infección, también ha generado saturación de los servicios de salud, incrementando las complicaciones y fallecimientos de otras enfermedades por la falta de oportunidad en la atención y el MM no es la excepción.

Abstract Multiple Myeloma (MM) is a heterogeneous oncological disease in its molecular component that in turn generates clinical variability, its risk is defined according to the Revised International Staging System, which considers: serious high levels of DHL and Beta2 microglobulina, low levels of albumin and the presence of some cytogenetic alteration, [del 17p13, t (14; 14), and t ( 14; 16)], the high-risk group is characterized by early relapse and short survival. At this time of the SARS-CoV-2 (COVID-19) pandemic, the management of patients with multiple myeloma has been indirectly affected by the lack of opportunity in diagnosis and management. In addition to there are data that suggest that the state of immunosuppression typical of the disease, combined with immunosuppressive and immunomodulatory therapy, makes them at high risk of complicating themselves and dying when they acquire the disease from COVID-19. However, there are no proper myeloma registries to corroborate this and in the COVID-19/cancer registries complications are reported mainly in lung cancer and those that are within 4 weeks of receiving intense chemotherapy. In Mexico and Latin America a brief survey only found isolated cases, the data has yet to be analyzed. The low frequency of patients with MM and COVID-19 is probably due to the care and isolation that is had with them beforehand. Since MM is a heterogeneous disease, we must continue to evaluate the risk at diagnosis and give full treatment to those at high risk, for this we must adjust the measures to reduce the risk of exposure to COVID-19, reduce visits to care units as much as possible, adjust first-line treatments according to the characteristics of each patient and monitor patients with intensive therapies and those requiring transplantation with tests for COVID-19 of hematopoietic progenitor cells. The COVID-19 pandemic is a catastrophe without a present, not only due to the morbidity and mortality of the infection, it has also generated saturation of health services, increasing complications and deaths from other diseases due to the lack of opportunity in care and Multiple Myeloma is no exception.

Prognostic tumor sequencing panels frequently identify germ line variants associated with hereditary hematopoietic malignancies.

Next-generation sequencing (NGS)-based targeted gene capture panels are used to profile hematopoietic malignancies to guide prognostication and treatment decisions. Because these panels include genes associated with hereditary hematopoietic malignancies (HHMs), we hypothesized that these panels could identify pathogenic germ line variants in malignant cells, thereby identifying patients at risk for HHMs. In total, pathogenic or likely pathogenic variants in ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, or TP53 were identified in 74 (21%) of 360 patients. Germ line tissue was available for 24 patients with 25 pathogenic or likely pathogenic variants with variant allele frequencies >0.4. Six (24%) of these 25 variants were of germ line origin. Three DDX41 variants, 2 GATA2 variants, and a TP53 variant previously implicated in Li-Fraumeni syndrome were of germ line origin. No likely pathogenic/pathogenic germ line variants possessed variant allele frequencies <0.4. This study demonstrates that NGS-based prognostic panels may identify individuals at risk for HHMs despite not being designed for this purpose. Furthermore, variants known to cause Li-Fraumeni syndrome as well as known pathogenic variants in genes such as DDX41 and GATA2 are especially likely to be of germ line origin. Thus, tumor-based panels may augment, but should not replace, comprehensive germ line-based testing and counseling.