The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of ...COVID-19 at F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an F-FDG-avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a "far-from-COVID-19" finding at PET/CT.
A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS)
conventional chemotherapy with rituximab (CHOP-R) as ...first-line therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13-year estimates of 77.0% and 36.8% for complete remission
no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (
<0.001), along with younger age (
=0.002) and female sex (
=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma. (Registered at clinicaltrials.gov identifier: 00435955).
Summary
The management of patients with Hodgkin lymphoma (HL) recurring after stem cell transplantation (SCT) and multiply relapsed disease remains challenging. We report on 41 such patients who ...received bendamustine hydrochloride, a bifunctional mechlorethamine derivative mechanistically unrelated to traditional alkylators, after a median of four prior chemotherapy lines, including SCT in 85% of cases. Bendamustine was given at doses of 90–120 mg/m2 every 21 or 28 d. At first assessment (2–4 cycles), the overall response rate (ORR) was 78% with 12 (29%) complete (CR) and 20 (49%) partial responses (PR). Upon treatment prolongation to 6–8 courses, 40% of PRs progressed, yielding a final ORR of 58% with 31% of CRs. Eight patients (two CRs, six PRs) were subsequently allotransplanted. Median progression‐free and overall survival exceeded 11 and 21 months respectively; complete responders displayed a median disease‐free survival above 9 months with a relapse rate of only 30%. Outcomes were independent of disease chemosensitivity, previous transplant and bendamustine dose‐intensity. No life‐threatening or unexpected adverse events occurred. Within the limits of a retrospective analysis and schedule heterogeneity, these results appear very encouraging and prompt prospective trials to confirm bendamustine as a valuable option in the palliative setting and in cytoreductive strategies before allotransplantation.
Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of patients (pts) with relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL). In previous studies, agents who ...target the PD-1 pathway have demonstrated to show substantial and durable response rates, with encouraging survival data and acceptable safety profile in this pts population. The Expanded Access Programme (EAP) provided the opportunity to treat pts before market availability of the drug. The aim of this analysis is to provide information about nivolumab use in a real world setting as well as in pts subgroups usually excluded from clinical trials.
Methods: Nivolumab was made available through the EAP conducted in Italy between July 2015 and December 2016 and treatment was delivered according to a prespecified protocol approved by ethical committees of participating centers. Pts aged ≥10 years, with histologically confirmed cHL who either failed or were not eligible for ASCT and failed brentuximab vedotin, were eligible if they had an ECOG Performance Status ≤2. Patients could have received prior allogenic transplantation if 6 or more months had lapsed since transplant and pts had no history of acute GVHD or extensive chronic GVHD. Nivolumab (3 mg/kg) was administered intravenously every 2 weeks until disease progression or unacceptable toxicity for up to 2 years. Pts included in the analysis received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.
Results: A total of 133 pts were enrolled across 40 Italian sites. Median age was 35 years (range: 15-82), 65% of pts were male and median number of previous lines of therapy was 4 (range 1-9), with 128 pts (96%) who had received prior brentuximab, 73 pts (55%) who had received prior autologous stem cell transplantation (ASCT) and 27 pts (20%) who had received prior allogenic stem cell transplantation (allo-SCT). At first tumor assessment, the objective response rate (ORR) was 68%, with 20 pts (15%) with complete response (CR), 71 (53%) with partial response (PR) and 18 (14%) with stable disease (SD). Among pts with no prior response to brentuximab (n= 74), ORR was 71%. At a median follow-up of 10.6 months (range 1-19), 1-year progression free survival (PFS) and overall survival (OS) were 61.4% and 89.0%, respectively. Overall, 68 pts (51%) discontinued treatment for the following reasons: 21 pts (13%) due to disease progression, 14 pts (10%) due to adverse events, 31 pts (23%) proceeded to transplantation (20 pts were bridged to allo-SCT and 11 pts to ASCT) and 2 pts for other reasons (physician decision). No treatment related deaths have been reported.
Conclusions: To date, this is the largest clinical experience with nivolumab in a real world setting in pts with R/R cHL. Data confirm results from pivotal trial demonstrating that nivolumab is a safe and effective therapy in this pts population, regardless of number and type of prior therapies. Importantly, about one quarter of pts were bridged to transplantation further supporting that PD1-blockade can overcome resistance to prior conventional treatments.
Santoro:Merck: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Zinzani:Celgene, Roche, Janssen, Gilead, Takeda, BMS, MSD, Servier, Sandoz, Mundipharma: Honoraria; Celgene, Janssen, Gilead, Roche, Takeda, BMS, MSD, Sandoz, Servier, Mundipharma: Speakers Bureau; Merck: Consultancy, Other: Advisory board. Corradini:Janssen: Honoraria; Roche: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Gilead: Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Specchia:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.
Introduction:
Management of elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL) is challenging. A simplified Comprehensive Geriatric Assessment (sCGA) based on ADL (Activity of Daily Living), ...IADL (Instrumental ADL) and CIRS-G (Comorbidity Index Rating Scale for Geriatrics) scales has demonstrated to be better than clinical judgement to stratify patients' outcome but has never been included in initial assessment. To further assess the impact of sCGA on patients' outcome, we conducted a prospective observational study on a large series of elderly patients with DLBCL.
Methods:
Patients were enrolled if 65 year old or older, with an untreated de novo DLBCL. sCGA was available at a web based platform that classified patients as FIT, UNFIT, and FRAIL, as shown in Table 1. Treatment choice was left at physician discretion. According to anthracycline dose, therapy was classified as curative (≥70% of full anthracycline dose), intermediate (<70%) or palliative (no anthracycline). Primary study endpoint was Overall Survival (OS).
Results:
From December 2013 to December 2017, 1353 patients have been registered by 37 centres and 1207 were eligible. Median age was 76 years (65-94), 68% had stage III-IV, and 55% had an International Prognostic Index(IPI) ≥3; 500 (42%), 304 (25%), and 403 (33%) were classified as FIT, UNFIT and FRAIL, respectively. Data on treatment were available in 1164 patients: rituximab was used in 96% of patients; treatment was curative in 89%, 53%, and 36% of FIT, UNFIT, and FRAIL patients, respectively; intermediate in 10%, 39%, and 31%, palliative in 0%, 8%, and 33% of patients.
The OS was available in 1158 out 1164 cases. With a median follow up of 30 months (1-59) 3y-OS was 64% (95% CI 61% to 67%). According to sCGA the OS was significantly different among the 3 geriatric groups. Correlation with OS was improved when sCGA was integrated with age < or ≥ 80 years to define 3 groups of patients (Table 2): FIT and UNFIT younger than 80 years (sCGA Group 1; 55%, 3 yr OS 75%), UNFIT ≥ 80 years and FRAIL younger than 80 years (sCGA Group 2: 28%, 3yr OS 58%), FRAIL ≥ 80 years (sCGA Group 3: 17%; 3yr OS 43%).
Univariable and multivariable analysis for OS was conducted using the 3 sCGA groups and other clinical and laboratory features. The 3 sCGA groups were shown as independent prognostic factors with IPI and with anemia (Hb < 12 g/dl). We used results of multivariable analysis to build a categorical prognostic index assigning different weights to prognostic features based on their Hazard Ratio (HR) (Table 3).
The Elderly Prognostic Index (EPI) was defined as the score obtained from the sum of the weights and allowed to define 3 risk groups: Low Risk (LR: score 0-1; 23% of patients); Intermediate Risk (IR; score 2-4; 48%); High Risk (HiR; score 5-7; 29%).
The 3 EPI risk groups had a different 3 year OS of 87%(95%CI 81-91), 69%(95%CI 63-73), and 42% (95%CI 36-49); HR for IR vs LR 2.57 (1.72, 3.84); HiR vs LR 6.21(4.17 -9.25), HiR vs IR 2.42 (1.91-3.05) (Figure1).
Regarding treatment modality, curative, intermediate and palliative therapies were adopted in 89%, 10%, and 1% of the LR group; 70%, 24%, 7% of the IR group, and 37%, 35%, 28% of the HiR group.
The model was internally validated by means of 1000 procedures confirming good performance (slope shrinkage 0.935 and c-Harrell 0.675 in validation sample compared with 0.682 in training sample).
The EPI was also tested in an external validation data set that was identified from the pivotal study of sCGA in DLBCL (N=172 patients, Tucci A. et al, Leuk Lymph, 2015) (Figure 1).
Conclusion:
Using data from this large prospective observational study on elderly DLBCL patients we were able to build a new prognostic index that allows to identify 3 risk groups with significant differences in terms of 3 years OS. The EPI is the first index that integrates geriatric assessment with clinical features and contributes to improving management and clinical research in elderly patients with DLBCL.
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Spina:Servier: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Sandoz: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other; Roche: Other: lecture fee; Teva: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; GILEAD: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Celgene: Other: lecture fee; BMS: Other: lecture fee; Sanofi Genzyme: Other: lecture fee; CTI: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Menarini: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee, Research Funding; Takeda: Other: lecture fee; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: lecture fee; Pfizer: Membership on an entity's Board of Directors or advisory committees. Merli:Janssen: Honoraria; Takeda: Honoraria, Other: Travel Expenses; Gilead: Honoraria; Mundipharma: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses. Cavallo:Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Ladetto:Roche: Honoraria; AbbVie: Honoraria; J&J: Honoraria; Celgene: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Chiappella:Celgene: Other: advisory board, Speakers Bureau; Janssen: Other: advisory board, Speakers Bureau; Servier: Other: advisory board, Speakers Bureau; Roche: Speakers Bureau; Teva: Speakers Bureau. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Ferrero:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau; Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees. Luminari:ROCHE: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant; GILEAD: Other: Lecturer; TAKEDA: Other: Travel Grant.
Abstract Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine–rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a ...phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008–2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43–86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale CIRS score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10.9%) had del11q and 18 (9.4%) del17p. The overall response rate (ORR) was 86.4%, with a complete remission rate of 28%. Patients with del17p had an ORR of 66.7%. After median follow-up of 24 months, the 2-year progression-free survival (PFS) was 69.9%; CIRS ≥7, immunoglobulin heavy-chain variable-region ( IGHV ) unmutated status, del17p and BR dose intensity <80% were independently associated with shorter PFS. Grade III or IV neutropenia, thrombocytopenia, and anaemia were observed in 25.9%, 15.4%, and 15.1% of patients, respectively. Twenty-four patients (8.6%) had severe infections. BR is also an effective and safe regimen for untreated CLL patients, outside of controlled clinical trials.
The incidence of non‐Hodgkin lymphoma in patients 80 years of age or older is 50 times higher than in 20‐ to 24‐year‐olds. Very elderly patients are often not treated with standard immunochemotherapy ...because of poor performance status, comorbidities, and toxicity concerns. We retrospectively analyzed data for 29 patients diagnosed with diffuse large B‐cell lymphoma or grade 3B follicular lymphoma and treated with rituximab in combination with nonpegylated liposomal doxorubicin between January 2010 and August 2015. The median age was 84 years. The overall 3‐year survival, cause‐specific survival, and progression‐free survival rates were 46%, 55%, and 44%, respectively. Among prognostic factors, only the achievement of complete remission strongly correlated with overall survival, cause‐specific survival, and progression‐free survival rates. Treatment caused very mild toxicity, without treatment‐related hospitalization or toxic deaths.
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