Role of Imaging in the Staging and Response Assessment of Lymphoma:Consensus of the International Conference on Malignant Lymphomas Imaging Working Group

This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for 18F FDG-avid lymphomas in clinical practice and late-phase trials

Phase 3 trial of ibrutinib plus rituximab in Waldenström's macroglobulinemia

En este estudio se evaluó el efecto de la adición de ibrutinib a rituximab en pacientes con macro-globulinemia de Waldenström, tanto en paciente que no habían recibido tratamiento previo como en aquellos con recidiva de la enfermedad. Se asignaron aleatoriamente 150 pacientes sintomá-ticos para recibir ibrutinib más rituximab o placebo más rituximab. El criterio principal de valoración fue la supervivencia libre de progresión, evaluada por un comité de revisión independiente. Los criterios de valoración secundarios clave fueron las tasas de respuesta, la mejoría hematológica sostenida desde el inicio y la seguridad. Se evaluó el estado mutacional de MYD88 y CXCR4 en muestras de médula ósea. A los 30 meses de seguimiento, la de supervivencia libre de progre-sión fue del 82% con ibrutinib-rituximab frente al 28% con placebo-rituximab (Hazard Ratio 0,20; P<0,001). El beneficio en el grupo de ibrutinib-rituximab sobre el grupo de placebo-rituximab fue independiente del genotipo MYD88 o CXCR4. La proporción de respuestas mayores fue más alta con ibrutinib-rituximab que con placebo-rituximab (72% vs. 32%, P<0,001). Hubo más pacientes con aumentos sostenidos en la concentración de hemoglobina con ibrutinib-rituximab que con placebo-rituximab (73% vs. 41%, P<0,001). Los efectos adversos más comunes (cualquier grado) con ibrutinib-rituximab, en especial reacciones relacionadas con la infusión, diarrea, artralgia y náuseas. Los efectos adversos grado ≥3 que fueron más frecuentes con ibrutinib-rituximab que con placebo-rituximab incluyeron fibrilación auricular (12% vs. 1%) e hipertensión (13% vs. 4%); los que ocurrieron con menos frecuencia incluyeron reacciones a la infusión (1% vs. 16%) y cual-quier grado de flare de IgM (8% vs. 47%). La tasa de hemorragia mayor fue la misma en los dos grupos de ensayo (4%). Gracias a este ensayo, que mostró beneficios en los pacientes con macroglobulinemia de Wal-denström para la combinación ibrutinib-rituximab frente a rituximab sólo (mejor supervivencia libre de progresión), tanto en pacientes de nuevo diagnóstico como en segunda línea, el fármaco se aprobó por la FDA. La EMA y la AEMPS, convirtiéndose en un estándar de tratamiento para la MW, con gran aceptación entre médicos y pacientes. Además se advirtió de la necesidad de to-mar actitudes activas frente a efectos secundarios relevantes como fibrilación auricular e hiperten-sión fueron más frecuentes con ibrutinib-rituximab, aunque el nuevo fármaco se vio favorecido por una menor frecuencia de reacciones a la perfusión y el fenómeno flare que sin dicho fármaco. El ensayo fue financiado por Pharmacyclics y Janssen Research and Development y se registró en ClinicalTrials.gov: NCT02165397.[EN]Single-agent ibrutinib has shown substantial activity in patients with relapsed Waldenström's macroglobulinemia, a rare form of B-cell lymphoma. We evaluated the effect of adding ibrutinib to rituximab in patients with this disease, both in those who had not received previous treatment and in those with disease recurrence. We randomly assigned 150 symptomatic patients to receive ibrutinib plus rituximab or placebo plus rituximab. The primary end point was progression-free survival, as assessed by an independent review committee. Key secondary end points were response rates, sustained hematologic improvement from baseline, and safety. The mutational status of MYD88 and CXCR4 was assessed in bone marrow samples. At 30 months, the progression-free survival rate was 82% with ibrutinib-rituximab versus 28% with placebo-rituximab (hazard ratio for progression or death, 0.20; P<0.001). The benefit in the ibrutinib-rituximab group over that in the placebo-rituximab group was independent of the MYD88 or CXCR4 genotype. The rate of major response was higher with ibrutinib-rituximab than with placebo-rituximab (72% vs. 32%, P<0.001). More patients had sustained increases in hemoglobin level with ibrutinib-rituximab than with placebo-rituximab (73% vs. 41%, P<0.001). The most common adverse events of any grade with ibrutinib-rituximab included infusion-related reactions, diarrhea, arthralgia, and nausea. Events of grade 3 or higher that occurred more frequently with ibrutinib-rituximab than with placebo-rituximab included atrial fibrillation (12% vs. 1%) and hypertension (13% vs. 4%); those that occurred less frequently included infusion reactions (1% vs. 16%) and any grade of IgM flare (8% vs. 47%). The major hemorrhage rate was the same in the two trial groups (4%). Among patients with Waldenström's macroglobulinemia, the use of ibrutinib-rituximab resulted in significantly higher rates of progression-free survival than the use of placebo-rituximab, both among those who had received no previous treatment and among those with disease recurrence. Atrial fibrillation and hypertension were more common with ibrutinib-rituximab, whereas infusion reactions and IgM flare were more common with placebo-rituximab. (Funded by Pharmacyclics and Janssen Research and Development; ClinicalTrials.gov number, NCT02165397 .).Janssen Research and Development PharmacyclicsJanssen Research and Developmen

Whimsical (Waldenstrom's Macroglobulinemia Study Involving CArt-wheeL): A Global Patient-Derived Data Registry Capturing Treatment, Quality of Life and COVID-19 Data

Introduction: Patient-derived data can increase breadth of knowledge in rare cancers like Waldenström's Macroglobulinemia (WM), including patient-reported outcomes (PROs). WhiMSICAL (Waldenström's Macroglobulinemia Study Involving CArt-wheeL) is the only global registry capturing patient-derived data for hypothesis generation in WM. Rapidly adaptable, it has been amended to capture Coronavirus Disease 2019 (COVID-19) data. Methods: An ethically-approved WM-specific extension to www.cart-wheel.org, an online rare cancer database for patient-derived data, was developed by clinician and patient investigators. Participants complete consent, and enter symptom, pathology, treatment and PRO (EORTC-QLQ-C30, Impact of Event Scale-6) data online. Recruitment strategies utilizing social media tools are driven by the International Waldenström's Macroglobulinemia Foundation investigators. A validation study compared patient-entered data with data-manager-entered data in the Australia & New Zealand Lymphoma & Related Diseases Registry (LaRDR). To capture the impact of COVID-19, additional questions on COVID-19 testing, symptoms and therapy, as well as effect on WM management in those without COVID-19, were included in April 2020. Results: 453 patients from 19 countries have been recruited, predominantly from USA (46%) and Australia (25%), with male predominance (62%). At diagnosis, median age was 61 (range 24-83), median IgM 2620 mg/dL (IQR 1320-3850 mg/dL, n=175) and median hemoglobin 11.4 g/dL (IQR 9.5-12.9 g/dL, n=181). Of the 365 (81%) patients providing symptoms at diagnosis, fatigue/muscle weakness was most common (46%) and 30% were asymptomatic. Using the Impact of Event Scale for symptoms of post-traumatic stress disorder (PTSD) resulting from a cancer diagnosis, the mean score among 387 patients was 5.9 (no stress=0, maximal stress=24), with 39/387 (10%) scoring >13 (PPV 94% for PTSD, Thoresen et al, 2010). This proportion did not increase for scores entered after March 1st, 2020 - 12/123 (10%) - when the COVID-19 pandemic became a global crisis. Marked treatment variation was noted, with 47 different first-line therapeutic combinations documented by 302 patients. Median time from diagnosis to first treatment for USA patients was 48 days (IQR 13-404, n=133) vs Rest of World (ROW) 176 days (IQR 20-885, n=163), (p=0.01). At median follow up of 38.5 months, first-line bendamustine rituximab had superior time to next treatment outcomes compared to other first-line therapies: rituximab monotherapy, dexamethasone-rituximab-cyclophosphamide and Bruton tyrosine kinase inhibitors (BTKi, Figure 1). 51 patients exposed to BTKi had a trend to higher EORTC QLQ-C30 global scales, mean 78.6±17.7, compared to 148 not exposed: mean 73.4±22.6 (p=0.13), despite higher treatment burden: median lines of treatment 2 (IQR 1-4) and 1 (IQR 1-2), respectively (p83%. 188/453 (42%) participants responded to the impact of COVID-19 questions; 75/188 (40%) had reduced face-to-face reviews, 4/188 (2%) had delays to starting treatment and 57/188 (30%) documented no impact. Of the 188 respondents, 23 (12%) had COVID-19 testing, with two returning a positive result and neither requiring hospitalization. Conclusion: WhiMSICAL is a robust, rapidly adaptable, global patient-derived data platform, providing insight into patient symptoms, real-world therapies and PROs. It is a scientific, ethically-approved portal for contributing the patients' voice in this rare lymphoma