ALBERT

Description: Abstract 4957 Background Over 40% of patients with the most common lymphoid malignancy worldwide, DLBL, are over the age of 70. Although R-CHOP is inarguably the mainstay of therapy for DLBL patients, a significant number of elderly patients do not tolerate the regimen due to underlying frailty and/or co-morbidities. Most elderly patients with significant co-morbidities have limited treatment options and are not offered anthracycline-containing chemotherapy due to concerns regarding toxicity. Here we describe our single center experience with CEEP, a lower intensity regimen for elderly patients with newly diagnosed or relapsed DLBL whom are deemed inappropriate for CHOP-based chemotherapy. Method All patients 〉70 years old (median 78.5, range 71 – 85) with histologically proven DLBL treated with CEEP ± Rituximab (R) at Royal Prince Alfred Hospital from 2000 to 2010 were retrospectively reviewed. Modified CEEP, Cyclophosphamide 300mg/m2 Day 1 (D1) and D15, Epirubicin 50mg/m2 D1 and D15, Etoposide 100mg/m2 D1 and D15, and Prednisolone 50mg D1-D5 (reduced dose from original CEEP protocol) was administered every 2 weeks. Rituximab 375mg/m2 (when approved for use in Australia) was administered every 28 days. As per institutional protocol, all patients received Bactrim prophylaxis for Pneumocystis. Baseline characteristics, Charlson Comorbidity Index, Revised International Prognostic Index (RIPI), the number of CEEP cycles, treatment response and toxicity from treatment were identified and reviewed. Results A total of 22 patients were identified, 10 were male. 15 received CEEP as initial therapy, and 7 for relapsed disease. 23% (n=5) had an ECOG score ≥ 2. 55% (n=12) had RIPI ≥ 3. All patients had a Charlson Comorbidity Index ≥ 2, with 23% (n=5) ≥ 5, which was considered sufficient to preclude conventional CHOP-based chemotherapy. Median cardiac ejection fraction was 62% (range 55 – 85%). 73% (n=16) received Rituximab and 50% (n=11) received primary GCSF prophylaxis. The median number of CEEP ± R cycles was 6 (range 2 – 9 cycles). 5% (n=1) required dose reduction and 9% (n=2) required delays in treatment due to haematological toxicity. Median follow-up was 10.0 months (range 1 – 92.7 months). At completion of therapy, complete responses (CR) were demonstrated in 10 patients (45%), with partial responses (PR) seen in 32% (n=7). 18% (n=4) demonstrated progressive disease (PD) despite therapy. Of the 7 patients with relapsed disease prior to CEEP ± R, CR was seen in 2 cases, both of whom had previous exposure to R-CVP (cyclophosphamide, vincristine, prednisolone) chemotherapy. At most recent follow up, 32% (n=7) have remained in CR with a median follow up period of 28.1 months (range 13 – 92.7 months), 36% (n=8) had disease progression, 9% (n=2) demonstrated stable residual disease, while 23% (n=5) have died. Of the 5 deaths, 3 were attributed to progressive DLBL. The other deaths were a result of complications following further salvage chemotherapy. Grade 3 – 4 haematological toxicity was observed in 72% (n=16) of patients. Febrile neutropenia occurred in 41% (n=9). Overall, 50% (n=11) required at least one re-admission to hospital. Non-haematological grade 3 – 4 toxicity was detected in 2 patients, one of whom suffered unstable angina in the setting of anaemia, the other an acute cerebrovascular event in the setting of new atrial flutter post-chemotherapy. Discussion Although limited by a small sample size, our retrospective single center experience demonstrates that CEEP ± R chemotherapy can be administered to elderly patients with significant co-morbidities. Our cohort was all aged 〉70, with medical co-morbidities leading to the unsuitability of conventional CHOP-based therapy. Whilst an overall response rate of 77% (CR + PR) was observed, on prolonged follow up, 32% of patients remained in CR. Significant haematological toxicity (72%) and infectious complications (41%) were observed, however no deaths were directly attributed to the chemotherapy. Future prospective studies are required to further evaluate the safety and efficacy of R-CEEP in the elderly. Disclosures: No relevant conflicts of interest to declare.

Description: 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. Disclosures Warden: Janssen Cilag: Other: Personal fees for photoshoot event. Opat:CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZenca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Research Funding. D'Sa:Sanofi: Honoraria; BeiGene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Kersten:Takeda: Research Funding; Roche: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Kite/Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Miltenyi Biotech: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen/Cilag: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); MSD: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Olszewski:Genentech, Inc.: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Research Funding. Harrington:Calithera Biosciences: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current equity holder in publicly-traded company; BeiGene: Current equity holder in publicly-traded company; Gilead: Current equity holder in publicly-traded company; Idera Pharmaceuticals: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company. Trotman:Takeda: Research Funding; PCYC: Research Funding; F. Hoffmann-La Roche: Research Funding; Celgene: Research Funding; BeiGene: Research Funding.