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Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Introduction The comprehensive geriatric assessment (CGA) in older patients with cancer is the gold standard to identify robust, frail or poor prognosis patients according Balducci classification. In Spain, a new proposal of a specific Geriatric Assessment in Hematology (GAH) scale has been designed and validated in patients with hematologic malignancies such as MDS/AML, multiple myeloma and CLL. The GAH scale has not been explored in patients with lymphoma. In this study, we have analyzed the utility of using the GAH scales in patients with hematologic malignancies, mostly lymphoma patients. Patients and methods. From March 2016 and September 2017, patients with hematologic malignancies were prospectively referred to the Geriatric Oncology clinic after a frailty screening test using G8 scale and with score Results Of the 96 patients referred aged 70 years or over, 41 were males (42.7%) and 55 females (57.3%), the median age was 79 years (range, 70-89), and with the diagnosis of lymphoma in 53 patients (55.2%), multiple myeloma in 23 patients (24.0%), CLL in 13 patients (13.6%), MDS/AML in 5 patients (5.2%) and CML in 2 patients (2.0%). Seventy-five patients (78.1%) had good performance status with ECOG score 0-1. Regarding frailty, 20 patients (20.8%) had a score of 15 points or over at G8 scale and 76 patients (79.2%) were identified as frail because of a score of 14 points or below. Regarding comorbidities, the median CIRS-G score was 9 (range, 4-20). After the GAH scale assessment, the median number of domains affected in robust patients was 2 (1-4) and in frail patients was 4 (3-5) (p=0.0001). In the ROC curve, with an AUC of 0.7595 and a likelyhood ratio of 9, the cut-off in this series was 2 domains with impairment, with a sentivity of 13.79% and a specificity of 92.5% (p= 0.0003). Using a correlation factor for each domain, the mean score at GAH scale in robust patients was 26 points and in frail patients was 42.5 points (p=0.0038). In the ROC curve, with an area under the curve of 0.7026 and a likelihood ratio of 2.04, the cut-off value to identify robust vs frail patients was 33 points in the GAH scale, with a sensitivity of 77.5% and a specificity of 62.07% (p=0.0043). Analyzing the eight domains explored in the GAH scale, robust patients according CGA had less risk of polypharmacy of 31.25% vs 81.48% in frail patients (OR 0.1033, 95% CI 0.0472-0.2541) (p Mean G8 score were similar between robust (11.68) and frail (11.04) patients (p=n.s.) among all patients with score below 14 points. Robust patients had less comorbidities according to CIRS-G scale, with a median of 9 vs 11 points (p=0.0001). There was correlation between CIRS-G and ECOG with G8 score, not found in previous studies. There is a correlation between the brief comorbidity assessment in the GAH scale with CIRS-G score. Among patients identified as not having comorbidities, the median CIRS-G score was 9 vs 13.5 among patients with comorbidities according the GAH scale (p Conclusions. The GAH scale is a valid tool for patients with hematologic malignancies, including patients with lymphoma, in order to classify patients according frailty phenotype. All domains explored in GAH scale were impaired with higher frequency in frail patients. Robust patients had less comorbidities and better performance status. The brief comorbidities assessment in the GAH scale correlates well with the CIRS-G. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Abstract 3698 Poster Board III-634 Introduction Bendamustine (B) is a purine analog/alkylator hybrid that has demonstrated clinical activity in relapsed indolent non-Hodgkin lymphoma (NHL), including those refractory to other alkylating or purine analog agents, chronic lymphocytic leukemia (CLL) and multiple myeloma patients. Bendamustine is currently licensed in Germany and Switzerland for use in NHL and CLL, and in evaluation process by European Medication Agency (EMA) in other countries. Aim Retrospective analysis of efficacy and toxicity of bendamustine as a single-agent or in combination for NHL and CLL treatment in the setting of compassionate use in Spain. Retrospective analysis of efficacy and toxicity of bendamustine as a single-agent or in combination for NHL and CLL treatment in the setting of compassionate use in Spain. Retrospective analysis of efficacy and toxicity of bendamustine as a single-agent or in combination for NHL and CLL treatment in the setting of compassionate use in Spain. Patients and methods Patients with relapsed or refractory NHL or CLL after at least 1 prior treatment regimen were eligible. Any bendamustine regimen was included. Results 91 patients(pts) from 18 institutions were included in the registry. The median age was 69 years (range: 36-88); male: 58%. Histology: 30 pts CLL; 16 pts aggressive NHL: pts (13 mantle cell lymphoma and 3 diffuse large B-cell lymphoma); 45 indolent NHL: (36 follicular lymphoma, 6 extranodal marginal zone B-cell lymphoma of MALT type and 3 lymphoplasmocytic lymphoma); ECOG/PS 0-1: 73%; Ann Arbor III-IV: 79% and IPI score >3: 48% in NHL, and Binnet B-C in CLL: 96%. Median time from diagnosis to Bendamustine treatment was 4,6 years (range 1-19,2) and median prior treatment regimens was 3 (range 1-11). 31 pts were refractory to prior treatment. The most frequent used regimen was Rituximab plus B (RB) independently of the histology (see table 1). Median number of Bendamustine cycles was 3 (range 1-7). 322 cycles of B were administered. 60% of de pts had adverse events grade 3-4, being hematologic toxicity the most frequent adverse event (54% neutropenia, 33% leucopenia, 29,7% thrombocytopenia, and 20% anemia). 15% cycles of B required pts admission in hospital. Sixty-nine pts were assessable for response at the time of analysis. Response rate are showed in table 1. 22 pts died (7 infection, 11 progression, 2 infection plus progression, 1 infection plus respiratory insufficiency and 1 isquemia). Table 1. Conclusions The most common regimen was Bendamustine at dose 90 mg/m2 associated with rituximab. Treatment with B produced a high response rate, independently of the histology in this population of heavily pretreated NHL and CLL pts, including refractory to prior therapies. Treatment with B produced durable objective responses with acceptable toxicity in this population of heavily pretreated NHL and CLL pts, including refractory to prior therapies. Updated data will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Background. Neutropenia is a common toxicity in patients (pts) with lymphoma (lymph) who receive myeloablative chemotherapy (CT). It frequently leads to CT delays and dose reductions, potentially compromising the clinical outcome. Granulocyte colonystimulating factors (G-CSFs) represented a major development in the prevention of this disorder. Current European and US guidelines (2006) recommend primary prophylaxis with G-CSF for patients at overall ≥20% risk of febrile neutropenia (FN) due to CT and patient-related factors. Methods. A multicentre, prospective, observational study, in adult pts with lymph initiating a new CT regimen with at least 4 planned cycles, assessing the incidence of grade 3–4 neutropenia (G3–4N) [defined as absolute neutrophil count Results. This interim analysis contains data from 270 consecutive lymph pts (300 pts per protocol) from 31 Spanish centres from November 2005 to November 2007. Pts were 53.3% male, median age 57.5 years (range: 19–85), 87.0% ECOG 0-1 and 60.9% III–IV stage (43.6% IV stage). 71.8% of lymph pts were treated with CHOP-based CT (83.0% R-CHOP). G-CSF was used in 83.9% of pts (76.8% primary prophylaxis (PP), 23.2% secondary prophylaxis (SP)). The G-CSF received was 49.1% filgrastim and 50.9% pegfilgrastim. Global incidence of G3-4N over the first four cycles was 39.9%. The G3-4N incidence was 39.6% in pts treated with pegfilgrastim while it was 52.3% in pts treated with filgrastim. Pts treated with PP had an FN incidence of 15.4% while the incidence was 22.0% in those receiving SP. Full dose on schedule (FDOS) [defined as ≤ 15% dose reduction and ≤ 3 days dose delay] was achieved in 65.1% of pts treated as PP and 60.8% of pts treated as SP. Conclusion. This study of clinical practice suggests that current guideline recommendations on the use of G-CSF PP with CT are becoming widely adopted in Spain. In patients receiving CT with intermediate/high FN risk, G-CSF PP and pegfilgrastim prophylaxis seemed to reduce neutropenia events compared with SP and Filgrastim. PP also improved the delivery of CT at full dose on schedule.

Background and objective Fludarabine in combination with cyclophosphamide (FC) plus rituximab (R) is an effective treatment for newly diagnosed as well as relapsed follicular lymphoma (Tam 2004; Keating 2005; Sacchi 2007). Maintenance treatment with R, after different induction treatments, improves overall and progression-free survival (Forstpointner 2006; van Oers 2006). Therefore, we aimed to evaluate the efficacy and safety of the FC-R regime followed by maintenance doses of R. Patients and Methods We present an intermediate report of the one-arm study in which 75 previously untreated patients with a diagnosis of follicular non-Hodgkin’s lymphoma in Ann Arbor stage II–IV were included between October 2004–2006. Seventy four were assessed for safety after receiving at least one FC-R dose (F: 3x25 mg/m2 and C: 1 g/m2; R: 375mg/m2), and 72 for response to treatment. Patients aged 53.4 years in average, one in five showed bulky disease and 72.2% Ann Arbor IV staging. FLIPI index determined 23.9% patients with low (0–1) score, 38% with intermediate (2) and 38% with poor score (3). A total of 47 patients presented some molecular alteration in PB or BM. Results Induction therapy was delivered throughout 4–6 courses, resulting in 91% complete responses (CR) and 9% partial responses (PR) (Table 1). From the patients who presented monoclonal population at diagnosis, 40 were evaluated for molecular response after induction and only 1 remained MDR positive for bcl2/IgH. Overall survival (OS) at 24 months was 87.5%, and two patients presented progressive disease within this period. The median OS has not been reached at this evaluation. To the date, 262 adverse effects grade 3–4 (32.6%) have been documented (80.9% neutropenias) and 80 infectious complications were recorded (23.8% grade 3–4). Three patients died from respiratory diseases, two from acute leukemia, and six from other causes. Table 1 EVOLUTION OF RESPONSE Evaluated Response at End of Induction Therapy Evaluated Response Post-Course 3 Assesable End Ind. (n=67) Missing End Ind. (n=5) CR: complete response; uCR: unconfirmed CR; PR: partial response; NE: not evaluated; WD: withdrawn; EX: exitus. Assesable PC3 (n=70) CRITERIA CR PR NE WD EX 14 CR 12 - 1 1 - 32 uCR 31 - 1 - - 24 PR 16 6 - - 2 2 Missing PC3 (NE) 2 - - - - 72 Total 61 6 2 1 2 Conclusions The FC-R has proven a potent antitumoral activity in untreated follicular lymphoma patients, rendering very high clinical and molecular responses. However, as reported in similar studies (Hochster 2007 ASCO), the high incidence of prolonged neutropenias and lymphopenias developed as consequence of the chemotherapy regime, questions the safety of the induction treatment.

Objectives. To evaluate clinical efficacy, molecular response and safety following the use of a regimen of fludarabine (25 mg/m2 x 3 days) Cy (1g/m2 x 1 day) and Rituximab (375 mg/m2/ x 1 day) (FCR)x 6 cycles, followed by maintenance with rituximab (375 mg/m2/week/x 4 weeks every 6 months x 2 years). (LNHF-03 Study). Patients and methods. Seventy-five (75) patients with a diagnosis of follicular NHL were included in the study between October 2004 and January 2006. The median age was 54 years (30–75). Twenty-one per cent (21%) of the patients had bulky disease. According to the FLIPI index: (0–1): 22.6%; 2: 40,3%; 3: 37,1%. Minimal residual disease (MRD): A clonal population on diagnosis was identified by means of the bcl–2/IgH major and minor rearrangement study by means of quantitative PCR rearrangements of the Igs by means of fluorescent PCR. Subsequently, samples were studied following the induction treatment and during the maintenance treatment. The analysis is performed in the 70 patients that completed the six induction regimens and were evaluated. Results. 64/70 patients were given the six cycles planned (91%). The presence of persistent cytopenia limited the cycles given in the other 6 patients to 4 or 5. Three hundred and thirty-eight (338) adverse effects were documented in the 414 cycles given to the 70 patients evaluated, almost all of them being mild, and 26 severe (degree 3–4), and almost all the cases were neutropenias. Infectious complications were frequent and many were severe: herpes zoster (5), pneumonia (5), cerebral toxoplasmosis (1), aspergillosis (1), infection by CMV (2). One patient developed erythroleukaemia within the first year following completion of the treatment. Three patients died ( CMV + aspergillosis, pneumonia, erythroleukaemia). 86% of the patients reached CR following induction, 6% unconfirmed CR and 8% partial response. On diagnosis, a clonal population was identified in 63% (45/71) of the cases. Of these 45 patients, samples are available following induction treatment in 35 cases. The molecular disease was negativised in all the cases, except one case with persistence of positive bcl2/IgH (0.3% as opposed to diagnosis) and is in uncertain CR. Of the 34 cases with negative ER, 32 are in CR or uncertain CR and 2 PR. Conclusions. The FCR regimen has proven to have a potent antitumoral activity in recently diagnosed follicular lymphoma patients with very high clinical (86% CR) and molecular (95%) responses. The immunosuppression caused is profound, with the appearance of opportunistic infections, and in some cases prolonged lymphopenias and neutropenias that call for future assessment and follow-up.