Limited benefit of additional contrast-enhanced CT to end-of-treatment PET/CT evaluation in patients with follicular lymphoma

AbstractDespite follicular lymphoma (FL) is frequently characterized by a moderate increase of glucose metabolism, PET/CT examinations provides valuable information for staging and response assessment of the disease. The aim of the study was to assess and compare the diagnostic performance of PET/ldCT and PET/ceCT, respectively, in evaluating FL patients at the end of treatment. Fifty FL consecutive patients who underwent end-of-therapy PET/CT with both ldCT and ceCT were analyzed. Two blinded observers independently assessed PET/ldCT and PET/ceCT applying the Deauville score (DS) and Lugano classification criteria. PET imaging obtained after the end-of-treatment (EoT) was classified as showing PET and ce-CT matched response (concordant imaging group, CIG) or PET and ce-CT unmatched response (discordant imaging group, DIG). Relapse rate and Event-Free Survival (EFS) were compared between CIG and DIG patients. Overall, no differences in metabolic response classification were observed between PET/ldCT and PET/ceCT. In 13 (26%) patients PET/ceCT identified additional FDG-negative nodal lesions in mesenteric, retroperitoneal and iliac regions. However, in all cases, final DS remained unchanged and the additional results did not modify the following therapeutic decision. Among patients, who obtained complete metabolic response a comparable rate of relapse was registered in DIG 3/13 (23%) and CIG subgroups 5/20 (25%) [p = 0.899]. In all 3 DIG cohort patients who relapsed the recurrent disease involved also, but not exclusively, PET negative lymph nodes detected by ceCT. In overall population metabolic response defined by PET/ldCT predicted EFS [76% (group of patients with metabolic response) vs 35% (group of patients with residual disease), p = 0.0013] significantly better than ceCT-Based response assessment [75% (group of patients with complete response) vs 53% (group of patients with residual disease), p = 0.06]. Our study demonstrates a negligible diagnostic and predictive value of ceCT performed in addition to standard 18FDG PET/ldCT for EoT response evaluation in FLs. PET/ldCT should be performed as first-line imaging procedure, also in patients with prevalent abdominal and pelvic involvement, limiting the acquisition of ceCT in selected cases. This tailored approach would contribute to avoid useless radiation exposure and preserve renal function of patients.

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Limited Benefit of Additional Contrast-Enhanced CT To End-of-Treatment PET/CT Evaluation In Patients With Follicular Lymphoma

10.21203/rs.3.rs-562796/v1 ◽

2021 ◽

Author(s):

Gaetano Paone ◽

Mariana Raditchkova-Sarnelli ◽

Teresa Ruberto-Macchi ◽

Marco Cuzzocrea ◽

Emanuele Zucca ◽

...

Keyword(s):

Follicular Lymphoma ◽

Metabolic Response ◽

Response Assessment ◽

Moderate Increase ◽

Comparable Rate ◽

Contrast Enhanced Ct ◽

End Of Treatment ◽

Pet Ct ◽

Ct Evaluation ◽

Line Imaging

Abstract Purpose: Despite follicular lymphoma (FL) is frequently characterized by a moderate increase of glucose metabolism, PET/CT examinations provides valuable information for staging and response assessment of the disease. The aim of the study was to assess and compare the diagnostic performance of PET/ldCT and PET/ceCT, respectively, in evaluating FL patients at the end of treatment. Methods: Fifty FL consecutive patients who underwent end-of-therapy PET/CT with both ldCT and ceCT were analyzed. Two blinded observers independently assessed PET/ldCT and PET/ceCT applying the Deauville score (DS) and Lugano classification criteria. PET imaging obtained after the end-of-treatment (EoT) was classified as showing PET and ce-CT matched response (concordant imaging group, CIG) or PET and ce-CT unmatched response (discordant imaging group, DIG). Relapse rate and Event-Free Survival (EFS) were compared between CIG and DIG patients. Results: Overall, no differences in metabolic response classification were observed between PET/ldCT and PET/ceCT. In 13 (26%) patients PET/ceCT identified additional FDG-negative nodal lesions in mesenteric, retroperitoneal and iliac regions. However, in all cases, final DS remained unchanged and the additional results did not modify the following therapeutic decision. Among patients, who obtained complete metabolic response a comparable rate of relapse was registered in DIG 3/13 (23%) and CIG subgroups 5/20 (25%) [p = 0.899]. In all 3 DIG cohort patients who relapsed the recurrent disease involved also, but not exclusively, PET negative lymph nodes detected by ceCT. In overall population metabolic response defined by PET/ldCT predicted EFS (76% vs 35%, p = 0.0013) significantly better than ceCT-Based response assessment (75% vs 53%, p = 0.06). Conclusion: Our study demonstrates a negligible diagnostic and predictive value of ceCT performed in addition to standard 18FDG PET/ldCT for EoT response evaluation in FLs. PET/ldCT should be performed as first-line imaging procedure, also in patients with prevalent abdominal and pelvic involvement, limiting the acquisition of ceCT in selected cases. This tailored approach would contribute to avoid useless radiation exposure and preserve renal function of patients.

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Functional Imaging for Therapeutic Assessment and Minimal Residual Disease Detection in Multiple Myeloma

International Journal of Molecular Sciences ◽

10.3390/ijms21155406 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5406 ◽

Cited By ~ 1

Author(s):

Bastien Jamet ◽

Elena Zamagni ◽

Cristina Nanni ◽

Clément Bailly ◽

Thomas Carlier ◽

...

Keyword(s):

Multiple Myeloma ◽

Fdg Pet ◽

Metabolic Response ◽

Residual Disease ◽

Complete Response ◽

Therapeutic Assessment ◽

Complete Metabolic Response ◽

Pet Ct ◽

Fdg Pet Ct ◽

Minimal Residual

Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10−5 and 10−6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.

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Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7545 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7545-7545

Author(s):

Miguel Angel A. Canales Albendea ◽

Thomas A. Buchholz ◽

Koji Izutsu ◽

Takayuki Ishikawa ◽

Laura Maria Fogliatto ◽

...

Keyword(s):

Follicular Lymphoma ◽

Stage Iv ◽

Progression Free Survival ◽

Response Assessment ◽

Complete Response ◽

Primary Analysis ◽

Open Label ◽

Secondary Endpoints ◽

To Receive ◽

Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

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[18F]Fluoromethylcholine PET/CT for CNS lymphoma assessment: a new tool

F1000Research ◽

10.12688/f1000research.73232.1 ◽

2021 ◽

Vol 10 ◽

pp. 1137

Author(s):

Kirsty Marshall ◽

Bhupinder Sharma ◽

Thomas Millard ◽

Sahil Chhabda ◽

Fayed Sheikh ◽

...

Keyword(s):

Grey Matter ◽

Response Assessment ◽

Complete Response ◽

Cns Lymphoma ◽

Residual Tumour ◽

Alternative Mode ◽

Positron Emission ◽

Pet Ct ◽

Magnetic Resonance Imaging Mri ◽

Cns Lymphomas

Background Central nervous system (CNS) lymphomas are a rare subset of lymphoma, which are associated with a poor outcome. The gold standard for CNS imaging is with gadolinium-enhanced magnetic resonance imaging (MRI); however, there are a number of limitations, including some patients with small persistent abnormalities from scarring due to focal haemorrhage or from a previous biopsy, which can be difficult to discern from residual tumour. [18F]Fluoromethylcholine positron emission tomography–computed tomography (FCH-PET/CT) uses an analogue of choline, which due to the upregulation of choline kinase in tumour cells, allows increased uptake of FCH. As there is minimal background grey matter uptake of FCH, FCH-PET/CT can be used in CNS imaging and provide a useful tool for response assessment. Methods This is a cohort study, where we identified 40 patients with a diagnosis of primary or secondary CNS lymphoma between 1st November 2011 and 10th October 2019. Results 26 of the 40 patients (65%) had concordant results. Of the discordant results, 11 out of 14 had partial response (PR) on MRI but showed a metabolic complete response (mCR) on FCH-PET. The overall response rates (ORR) were similar between the two modalities (90% for MRI versus 95% with FCT-PET/CT). Conclusion We conclude that FCH-PET/CT is a reasonable alternative mode of imaging to gadolinium-enhanced MRI brain imaging, providing a new tool for assessment of CNS lymphoma.

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Preliminary Results from a Phase II Study of Response-Adapted Therapy with Copanlisib and Rituximab for Untreated Follicular Lymphoma

Blood ◽

10.1182/blood-2020-134115 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 39-40

Author(s):

Rahul Lakhotia ◽

Christopher Melani ◽

Jagan R. Muppidi ◽

Stefania Pittaluga ◽

James D. Phelan ◽

...

Keyword(s):

Supportive Care ◽

Follicular Lymphoma ◽

Systemic Therapy ◽

Conflicts Of Interest ◽

Residual Disease ◽

Complete Response ◽

Clinical Results ◽

Circulating Tumor Dna ◽

Molecular Profile ◽

Preliminary Results

Introduction Follicular lymphoma (FL) has a highly variable clinical course. Chemoimmunotherapy can induce durable remissions, but ~20% relapse early. The PI3K pathway is central to FL biology and multiple PI3K inhibitors (PI3Ki) are approved for FL, but the molecular profile of tumors most sensitive to PI3Ki is unknown. Further, PI3Ki are dosed indefinitely which contributes to toxicity and cost. Copanlisib is an IV inhibitor of PI3Kα and δ isoforms with high activity in relapsed FL. We hypothesized that patients with FL tumors most sensitive to PI3Ki will achieve deep and durable remissions after a fixed duration of copanlisib-based therapy. Here we report preliminary results of a response-adapted study using copanlisib and rituximab as frontline therapy for FL. Methods Pts with untreated grade 1-2, 3A FL, ≥stage 2, and any tumor burden are eligible if they meet criteria for need of systemic therapy that includes symptoms, increasing size of nodes, critical organ involvement, or impending organ compromise. No prior systemic therapy other than radiation is permitted. Frozen or archival tissue is required. Eligibility includes age ≥18 and adequate organ function unless involved by FL. Active HIV, CMV, Hep B or C, and autoimmune conditions requiring therapy are excluded. All pts receive PCP prophylaxis. Pts first receive copanlisib 60mg on days 1, 8, and 15 of a 28-day window to test activity of monotherapy. On-treatment tumor biopsies are optional after the window. Following the window, pts receive 6 cycles of copanlisib 60mg on days 1, 8, and 15 of a 28 day cycle along with rituximab 375mg weekly x 4 then on day 1 of each cycle. Streck tubes for circulating tumor DNA (ctDNA) are collected weekly during the window, after each cycle, and during surveillance. FDG-PET and CT scans are performed at baseline, after the window, and after cycles 3 and 6 to determine response. Patients with complete response (CR) after 6 cycles stop therapy. Patients with partial response (PR) after 6 cycles receive another 6 cycles of combination therapy with the copanlisib reduced to day 1 and 15 of each cycle. Non-responding patients will receive standard chemotherapy. The primary endpoint is the overall rate of CR with secondary endpoints of safety and duration of CR. Exploratory objectives include identification of a signature that predicts PI3Ki response. Results Ten pts have been enrolled and completed the copanlisib window. Median age was 50y (range, 28-77) including 3 (30%) over age 70. Seven (70%) pts had high-risk FLIPI scores ≥3 and two (20%) pts had Grade 3A FL. Comorbid conditions included prediabetes in 4 (40%) and hypertension in 4 (40%). All 10 (100%) pts had tumor reductions during copanlisib monotherapy with a median reduction of 41% (range 16-62%) (Figure 1). Four pts have completed 6 cycles of copanlisib and rituximab and all 4 (100%) have responded including 2 (50%) who achieved CR. In the two pts who achieved a PR after 6 cycles, one had a 90% tumor reduction and one had only persistent minimal residual disease in the bone marrow by flow cytometry. Toxicity was evaluated in 10 pts across 58 cycles and the most common have included rash (50%), diarrhea (50%) and mucositis (40%) which have all been G1 or G2 and successfully managed with supportive care and did not recur with subsequent cycles. One pt developed grade 3 neutropenia that responded to growth factors and did not recur. Four pts had dose delays due to rash (N=3) and lung infection (N=1). One pt had copanlisib reduced to 45mg due to recurrent rash and elevated liver tests. No pt has discontinued therapy. One pt required oral diabetic medications during therapy that were stopped after therapy completed. One pt had asymptomatic PCP pneumonia diagnosed during the copanlisib window prior to starting prophylaxis that was successfully treated while therapy continued. Conclusion Copanlisib is highly active in untreated FL and the first 10 (100%) patients all had tumor reductions after the first cycle of copanlisib monotherapy, including patients with high tumor bulk. Combination of copanlisib and rituximab can induce complete responses after only 6 cycles and without indefinite therapy. The safety profile includes rash and diarrhea that respond to supportive care and lessen on subsequent cycles. Updated clinical results from this ongoing trial (NCT03789240) along with the molecular profile of FL tumors will be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

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Improving the Definition of Response Assessment: Prognostic Value of Minimal Residual Disease Combined with PET/CT at Day 100 Post Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽

10.1182/blood-2020-142845 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Miguel Gonzalez-Velez ◽

Mariano Arribas ◽

Heidi E. Kosiorek ◽

Richard Butterfield ◽

Carlo Guerrero ◽

...

Keyword(s):

Board Of Directors ◽

Prognostic Value ◽

Residual Disease ◽

High Sensitivity ◽

Response Assessment ◽

Advisory Committees ◽

Pet Ct ◽

Definition Of ◽

Minimal Residual

Introduction: Response assessment at day 100 post Autologous Stem Cell Transplant (ASCT) is associated with long-term relapsed free survival (RFS) and overall survival (OS) in multiple myeloma (MM). The International Myeloma Working Group (IMWG) are the preferred criteria to define best response to treatment and define relapse. In the last years, response assessment has incorporated minimal residual disease (MRD) status -associated with improved RFS and OS (Munshi et al); and PET/CT combined with clinical characteristics -also associated with favorable outcomes (Zamagni et al. NCT01910987; MMY3033). The 2016 IMWG MRD criteria, combined imaging (PET/CT) plus next-generation sequencing (NGS) MRD-negative to define complete response (CR). To our knowledge, there is limited data examining the correlation and prognostic value of MRD and FDG-PET/CT at day 100 post ASCT in MM. IN this study, we aimed to determine the prognostic valued of MRD by NGS combined with PET/CT in RFS and OS status after high dose chemotherapy and ASCT in MM. Methods: Patients who underwent ASCT for MM at Mayo Clinic Arizona and had MRD and PET/CT data were included in the study. Clinical data was obtained via retrospective chart review. Cytogenetic risk (CyR) was classified using the mSMART criteria . Disease and ASCT related characteristics were compared by MRD status. MRD was measured by NGS on bone marrow aspirates using the previosly validated clonoSEQ ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) tracking the IgH, IgK and IgL rearrangements at a minimum sensitivity level of 10-5. MRD was defined by residual clonal cells per million nucleated cells as: negative= 0, borderline= 1-5, positive >5. PET/CT scans were performed locally at baseline and at day 100. Comparisons were performed using the chi-square test for categorical variables, Wilcoxon rank-sum test for continuos variables, McNemar's test and Cohens's Kappa for agreement measures. Results: A total of 103 patients had matched MRD and PET/CT assessment around day 100 (+/-9 days) and were included in the analysis. Median age at diagnosis was 62 years (range, 54-66 years), 71 patients (68.9%) were men. CyR was standard risk in 49 (47.6%), high-risk in 39 (37.9%) and unknown in 15 (14.6%) patients. Most 75 (72.8%) patients were MRD positive, 16 (15.5%) were MRD negative, and 12 (11.7%) borderline. The median main MRD clone detected was 64 (range 0-91,874). 70 patients (68%) and 33 (32%) had a negative and positive PET/CT respectively. The median follow-up time was 18 months (range, 13-31 months). At the time of data analysis, 10 patients (9.7%) had relapsed and only 4 (3.9%) had died. There was a high-correlation between MRD status and PET/CT, 31 patients (93.9%) with positive PET/CT were also MRD positive (p=0.0027). There were no statistical differences between PET/CT and CyR (p=0.95). We analyzed the correlation using the FREQ procedure (McNemars's test); there was a strong association between positive PET/CT and positive MRD in 31/33 patients (93.9%, high sensitivity), and low association for negative PET/CT the negative/borderline MRD in 26/70 (37.1%, low specificity; p<0.001). The agreement measure between the PET/CT and MRD using negative/borderline combined had a kappa of 0.23 (95% CI 0.11, 0.35) indicating a fair agreement beyond chance (Figure 1). PET/CT-CT was a statistically significant predictor of worse RFS (HR 3.53, 95%CI: 1.02-12.24, p<0.0337) and OS (HR 11.38, 95%CI: 1.18-109.56, p<0.0078) (Figure 2-3, respectively). MRD was not predictive of neither RFS (HR 1.72, 95%CI: 0.36-8.14, p<0.49) or OS (p<0.16). Conclusions: In conclusion, we demonstrate that the combination of MRD by NGS (clonoSEQ ®) and PET/CT at day 100 are complementary and have a high sensitivity (true positive rate) and fair correlation of agreement but low specificity (true negative rate). PET/CT was the best most sensitive technique to prognosticate RFS and OS. We did not find prognostic correlation of MRD with RFS and OS. However, our findings might be confounded by the low risk of relapse and death, a longer follow-up may demonstrate clinically important differences. Our results add evidence that MRD plus PET/CT improve the definition of CR in MM patients post ASCT. Prospective studies are needed to elucidate the optimal timing and role of combined MRD, PET/CT with other prognostic markers of clinical outcomes. Disclosures Larsen: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fonseca:Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy.

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Obinutuzumab plus lenalidomide (GALEN) in advanced, previously untreated follicular lymphoma in need of systemic therapy

Blood ◽

10.1182/blood.2021013526 ◽

2021 ◽

Author(s):

Emmanuel Bachy ◽

Roch Houot ◽

Pierre Feugier ◽

Krimo Bouabdallah ◽

Reda Bouabdallah ◽

...

Keyword(s):

Follicular Lymphoma ◽

Safety Profile ◽

Response Rate ◽

Metabolic Response ◽

Complete Response ◽

Tumor Burden ◽

Common Adverse Event ◽

Induction Treatment ◽

High Tumor Burden ◽

Grade 3

Obinutuzumab and lenalidomide (GALEN) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously-untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥ 18 years had ECOG PS ≤ 2, high-tumor burden, grade 1-3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8/15/22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/day, days 1-21, cycle 1; days 2-22, cycles 2-6) for 6 cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤ 12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary endpoint was complete response rate (CRR) after induction per IWG 1999 criteria. From October 2015 to February 2017, 100 patients were enrolled. CRR after induction was 47% and overall response rate (ORR) 92%. Post-hoc analyses per 2014 Lugano classification including patients with missing bone marrow assessments identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any-grade; 47% grade ≥ 3) but only 2% of patients presented febrile neutropenia; others were mainly grade ≤ 2. No other specific grade ≥3 toxicity occurred at a frequency higher than 3%. Overall, these results demonstrated promising clinical efficacy for the chemo-free backbone obinutuzumab and lenalidomide in previously untreated, high tumor burden FL patients. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered with ClinicalTrials.gov, number NCT01582776

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Assessment of therapeutic response of lymphoma patients by PET/CT

QJM ◽

10.1093/qjmed/hcab106.058 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Aya Y Ahmed ◽

Mona A Nagi ◽

Radwa H. El Sheikh

Keyword(s):

Therapeutic Response ◽

Imaging Modality ◽

Treatment Plan ◽

Response Assessment ◽

Response To Therapy ◽

University Hospital ◽

Lymphoid Tissues ◽

Cross Sectional ◽

End Of Treatment ◽

Pet Ct

Abstract Background Lymphoma compromises а histologically heterogeneous group of cancers derived from the cells of the immune system. The hallmark of the disease is the enlargement and proliferation of lymph nodes or secondary lymphoid tissues. Aim of the Work to evaluate the role of Positron emission tomography in the assessment of response to therapy in lymphoma patients: in particular, a five-point scale (Deauville criteria), which can be employed for early- and late-therapeutic response assessment. Patients and Methods This cross sectional study was conducted on 20 Patients with different types of lymphoma recruited and enrolled from Ain Shams university hospital. Results PET/CT and Contrast enhanced computed tomography were concurrent in results in 55% of cases during treatment and 75 % at the end of treatment with CT sensitivity of 61.1%, specificity of 92.2% and accuracy of 76.2% during treatment in comparison to 100 % sensitivity and specificity of PET/CT.While sensitivity of CT at end of treatment is 57.5% with specificity of 86.7% and accuracy of 71.6%. Conclusion PET/СT using 2-deoxy-2[18F]fluoro-D-glucose is considered one of the best oncologic imaging modality at the time being with valuable applications in lymphoma.It is very efficient with least possible pitfalls and false results compared to either of its components alone and to side by side reading of separately acquired PET and СT. It is becoming а standard modality for lymphoma providing а new vision to management and treatment plan.

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90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial

Journal of Clinical Oncology ◽

10.1200/jco.2011.41.1553 ◽

2013 ◽

Vol 31 (3) ◽

pp. 308-313 ◽

Cited By ~ 70

Author(s):

Christian W. Scholz ◽

Antonello Pinto ◽

Werner Linkesch ◽

Ola Lindén ◽

Andreas Viardot ◽

...

Keyword(s):

Follicular Lymphoma ◽

Phase Ii ◽

Residual Disease ◽

Standard Procedure ◽

Complete Response ◽

Molecular Response ◽

First Line ◽

Ibritumomab Tiuxetan ◽

Multicenter Phase

Purpose We report on a multicenter phase II trial of 90yttrium-ibritumomab-tiuxetan (90YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). Patients and Methods Fifty-nine patients with CD20+ FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received 90YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of 90YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. Results Six months after treatment with 90YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after 90YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). Conclusion 90YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after 90YIT appear to have long- lasting responses.

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Role of PET/CT As a Measure of Minimal Residual Disease (MRD) Negativity Among Patients with Myeloma Post Autologous Stem Cell Transplant (ASCT)

Blood ◽

10.1182/blood.v126.23.4202.4202 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4202-4202

Author(s):

Ajay K. Nooka ◽

Jonathan L. Kaufman ◽

A. Tuba Karagulle Kendi ◽

Yan Li ◽

Chikaodili O Obidike ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Residual Disease ◽

Standardized Uptake Value ◽

Response Assessment ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Pet Ct ◽

Lytic Lesions

Abstract Background: In the context of improved novel therapeutic anti-myeloma regimens using combinations of antibodies and other small molecules, measuring the efficacy of therapy is an ongoing challenge. Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC), polymerase chain reaction (ASO-PCR), next-generation sequencing are sensitive tests that are becoming more significant as improved therapies result in deeper responses, however challenges remain, such as standardizing these testing methods. 18F Fluorodeoxglucose Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that can provide essential information in diagnosis and management of MM. PET/CT has high sensitivity (80-90%) and specificity (80-100%) to detect MM lesions. PET/CT also has a recently acknowledged role in prognostic information. Standardized uptake value maximum (SUVmax) is a widely used PET/CT parameter for assessment of therapy response in a variety of cancers. Recent publication by Zamagni et al showed that in addition to the presence of three or more focal lesions, a maximum standardized uptake value (SUVmax) of over 4.2 and presence of extramedullary disease were negative prognostic factors. Our aim in this study was to evaluate the prognostic role of PET/CT in MM patients post ASCT at day 100 restaging. Methods: We have identified 130 myeloma patients that underwent autologous stem cell transplant (ASCT) from 09/2014 until 04/2015. Along with their hematologic restaging post-ASCT for response assessment per International Myeloma Working Group (IMWG) criteria, patients also underwent PET/CT for MRD assessment. After excluding 3 patients that underwent tandem transplants, and one patient that received stem cell boost, 102 patients were evaluable for the current analysis (24 patients did not undergo PET/CTs). We have done an exploratory analysis with previously described SUVmax cut off of <2.0 (Waheed S) and <4.2 (Zamagni E). Results: The median age of the patients that underwent ASCT was 64 years (range: 38-76 years). 77 pts (75%) received melphalan 200 mg/m2, 22 pts (22%) received melphalan 140 mg/m2, 2 pts received melphalan+bortezomib and 1 pt received BEAM regimen as conditioning regimen. Median time from day 0 to response assessment is 98 days (range: 55-189 days). Hematological restaging shows that 89% of patients achieved ≥VGPR (SCR: 46% and CR: 11%). 13 pts did not have prior lytic lesions while 89% had lytic lesions (one lesion: 4%, two lesions: 2% and multiple (≥3): 82%). PET/CT negativity was achieved among 63% of the patients. At SUV cut off of <2.0 and <4.2, PET/CT negativity was achieved among 64% of the patients and 83% of the patients respectively. Taking the patients that have achieved SCR, for the same cut offs, PET/CT negativity rates were 59% and 76% respectively (Table 1). Conclusions: Negative PET/CT rates post-ASCT are in accordance with previously published studies. With taking SUVmax as sole criteria for assessing MRD negativity, false positive PET/CT results will continue to remain a challenge. Although SUVmax is the most widely used PET/CT parameter, it has limitations. There are other PET/CT parameters mean or peak standardized uptake values (SUVmean, SUVpeak); metabolic tumor volume (MTV); total lesion glycolysis (TLG); standardized added metabolic activity (SAM); and, normalized standardized added metabolic activity (NSAM) used in clinical practice and research. These PET/CT parameters may have role as prognostic imaging probes in MM patients post ASCT. With longer follow up to assess PFS and OS, we can evaluate the prognostic impact of using PET/CT as MRD measure. Table 1. PET parameters and hematological responses Response Response rates PET positive PET negative PET positive (≥SUV 2.0) PET negative (<SUV 2.0) PET positive (≥SUV 4.2) PET negative (<SUV 4.2) SCR 46 19 27 19 27 11 35 CR 11 7 4 6 5 3 8 VGPR 34 9 25 9 25 3 31 PR 10 2 8 2 8 0 10 PD 1 1 0 1 0 1 0 ≥CR 57 26 31 25 32 14 43 ≥VGPR 91 35 56 34 57 17 74 Disclosures Nooka: Onyx Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Gleason:Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Lonial:Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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