Post‐treatment (not interim) positron emission tomography‐computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R‐HyperCVAD

Mato, Anthony R.; Svoboda, Jakub; Feldman, Tatyana; Zielonka, Tania; Agress, Harry; Panush, David; Miller, Mitchell; Toth, Patrick; Lizotte, Paul M.; Nasta, Sunita Dwivedy; Goldberg, Stuart L.; Chong, E A; Schuster, S.; Pecora, Andrew L.; Goy, André

doi:10.1002/cncr.26731

Cited by 45 publications

(35 citation statements)

References 41 publications

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“…Recent retrospective reports, however, suggest a relevance of PET in response assessment. [24][25][26] In our prospective study, a positive PET scan pretransplant was associated with a median PFS of ,2 years, significantly shorter than in the PET-negative cohort. The PETpositive PR group is of particular interest: according to the revised response criteria 27 , any PET-negative residual mass is compatible with CR.…”

Section: Discussionmentioning

confidence: 58%

“…In multivariate analysis (including MIPI-B, response by CT prior to transplant, and MRD after transplant), a positive PET scan before transplant was shown to be an independent predictor of PFS, EFS, and particularly OS. In retrospective studies, 25,26 a positive posttreatment PET scan also predicted early relapse. Our prospective PET-based results strongly suggest a value of this modality in the evaluation of response in MCL.…”

Section: Discussionmentioning

confidence: 96%

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Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

Kolstad

Laurell

Jerkeman

et al. 2014

Blood

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Y-ibritumomab-tiuxetan (Zevalin) to the highdose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), eventfree survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 96%

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

Kolstad

Laurell

Jerkeman

et al. 2014

Blood

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“…[13][14][15] In MCL, endof-treatment PET/CT is prognostic for PFS in non-transplant patients, both in a heterogeneously treated population and a population uniformly treated with R-HyperCVAD in the front-line setting. 16,17 The role of PET/CT continues to expand in the management of NHL, and despite prior uncertainty regarding its utility in indolent NHL, patients completing induction with chemoimmunotherapy and embarking on a maintenance regimen of rituximab who have a positive PET/CT appear to have inferior PFS at 42 months (32.9%) compared with PET/CT( À )patients (70.7%, Po0.001). 20 We present one of the first series to date evaluating the role of pre-transplant PET/CT in MCL.…”

Section: Discussionmentioning

confidence: 99%

“…16 In another series of MCL patients treated in the front-line with R-HyperCVAD without auto-SCT consolidation, a positive PET/CT at the conclusion of therapy was associated with a median PFS of 11.1 months, while the median PFS for patients with a negative PET/CT was not reached (P ¼ 0.0002). 17 Little is known, however, about the significance of PET/CT findings before auto-SCT in MCL. Therefore, we performed a retrospective study of patients with MCL and available pretransplant PET/CT at the Ohio State University (OSU) reviewed by a single nuclear medicine physician according to International Harmonization Criteria 18 to determine the association of PET/CT response with PFS and OS post auto-SCT.…”

Section: Introductionmentioning

confidence: 99%

Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle cell lymphoma

Cohen

Hall

Ruppert

et al. 2013

Bone Marrow Transplant

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Positron emission tomography/computed tomography (PET/CT)-positive findings before autologous SCT (auto-SCT) are associated with inferior PFS and OS in patients with relapsed Hodgkin's and diffuse large B-cell lymphoma. We classified pre-transplant PET/CT performed before auto-SCT as positive or negative to evaluate the impact of pre-transplant PET/CT in mantle cell lymphoma (MCL). In 29 patients, 17 were PET/CT( À ) and 12 were PET/CT( þ ). PET/CT( þ ) patients were younger (P ¼ 0.04), had lower MCL International Prognostic Index (MIPI, P ¼ 0.04) scores, but increased bulky adenopathy 45 cm (45% vs 13%, P ¼ 0.09). With a median follow-up of 27 months (range: 5-55 months), 7 patients relapsed (4 in the PET/CT( À ) group and 3 in the PET/CT( þ ) group) with 2 deaths in the PET/CT( þ ) group without a documented relapse. The estimated 2-year PFS was 64% (95% confidence interval (CI): 0.30-0.85) vs 87% (95% CI: 0.57-0.97) in PET/CT( þ ) and PET/CT( À ) patients, respectively (P ¼ 0.054). OS was significantly decreased in PET/CT( þ ) patients (P ¼ 0.007), with 2-year estimates of 60% (95% CI: 0.23-0.84) vs 100% in PET/CT( À ) patients. A positive pre-transplant PET/CT is associated with a poor prognosis in patients with MCL. Additional factors may impact the prognostic value of PET/CT, as several PET/CT( þ ) patients remain in remission.

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“…Two strategies have been evaluated to appreciate the quality of response in MCL: functional imaging [positron emission tomography (PET)] and MRD assessment. Retrospective studies of PET following R-hyper-CVAD induction showed a significant association between posttreatment PET positivity and outcome, whereas interim PET was not predictive (60). PET negativity before upfront ASCT was associated with superior PFS and OS in MCL (61) but not if induction was R-CHOP only (ref.…”

Section: Assessment Of Quality Of Response To Predict Outcomes: Mrd Amentioning

confidence: 99%

Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice

Avivi¹,

Goy

2015

Clinical Cancer Research

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Although mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma, proactive research efforts fueled by challenges in the management of MCL have led to an increase in median overall survival (OS) of 2.5 years in the mid 1990s to beyond 5 years nowadays. This improvement is due mostly to the use of dose-intensive strategies, particularly cytarabinecontaining regimens [with or without high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) consolidation], which are associated with deeper remission (and higher molecular complete response rate), as well as better salvage therapies. Along this line, MCL became the first lymphoma for which four novel agents have been approved in the relapsed/refractory setting: temsirolimus, lenalidomide, ibrutinib, and bortezomib (the last agent approved both in relapsed/ refractory disease and in first-line combination therapy). In addition, the use of rituximab maintenance has helped reduce relapse rates and improve outcome. However, in routine practice (i.e., outside clinical trials), the outcome of MCL remains overall unchanged with standard immunochemotherapy, and even after HDT-ASCT, most patients still relapse and frequently develop chemoresistance. The persistent lack of consensus for the treatment of MCL explains the rather impressive variability in management of these patients. The integration of newer therapies, either in combination with immunochemotherapy or as consolidation/maintenance postinduction, offers new opportunities for patients with MCL. This review highlights how such developments can help refine the current MCL paradigm.

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Post‐treatment (not interim) positron emission tomography‐computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R‐HyperCVAD

Abstract: These data do not support the prognostic utility of PET-CT in pretreatment and interim treatment settings. A positive PET-CT after the completion of therapy identifies a patient subset with an inferior PFS and a trend toward inferior OS.

Cited by 45 publications

References 41 publications

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle cell lymphoma

Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice

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