Back to Authors

Wagner‐Johnston, Nina D.

https://orcid.org/0000-0001-6529-9793

Mayo Clinic

Johns Hopkins Kimmel Cancer Center

Citations 35

Outcomes of Patients with Limited-Stage Plasmablastic Lymphoma
Hess, Brian , Giri, Anshu , Patel, Krina K. , Nowakowski, Grzegorz S. , Maliske, Seth , Hill, Brian T. , Garcia, Alex, Maddocks, Kami J. , Wagner‐Johnston, Nina D. , Messmer, Marcus , Alderuccio, Juan Pablo , Lossos, Izidore S., Nathan, Sunita , Portell, Craig A. , Ayers, Emily C. , Portell, Craig A , Park, Yeonhee , Link, Brian K. , Fortin, Sonia, Chavez, Julio C , Saeed, Hayder , Hanel, Walter G. , Kahl, Brad S. , Watkins, Marcus P. , Lossos, Izidore S. , Orellana‐Noia, Victor M. , Landsburg, Daniel J. , Castillo, Jorge J.

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 15-16

10.1182/blood-2020-138536 Get It

Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Castillo JJ, Am J Hematol. 2008) There has been a paucity of data suggesting that limited stage disease (Ann Arbor stage I-II) may have a more favorable prognosis. However, due to the rarity of this disease there have been no large-scale reviews to confirm this. Thus, many patients with limited stage disease are subject to the aggressive therapy recommendations based on the poor outcomes of PBL patients as a whole. (Loghavi S, J Hematol Oncol. 2015; NCCN Guidelines, version 2.2020; Al-Malki MM, BBMT. 2014) We attempted to determine the treatment patterns and outcomes of patients with limited stage PBL. Methods: We conducted a multi-center (13 US academic centers) retrospective study of patients with limited stage (Ann Arbor stage I-II) Plasmablastic lymphoma. Determination of limited stage and diagnosis of PBL was determined by the investigators at each individual center. Patients diagnosed between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcomes data were extracted by retrospective chart review. Kaplan Meier was utilized for time to event analysis. Results: Baseline characteristics are included in table 1. A total of 80 patients were identified with limited stage disease. With a median follow up of 34 months the 3-yr Progression free survival (PFS) and overall survival (OS) was 71.9% and 78.7% respectively (Figure 1A and 1B). Patients that received frontline chemotherapy with (n=29) and without RT (n=36) had a 3-yr PFS and OS of 84.6% and 96.2% as compared to 64.5% and 70.8%, respectively (Figure 2A and 2B; Figure 3A and 3B). The Hazard ratio (HR) for PFS and OS for chemo (reference) vs chemo-RT was 0.47 (95% CI 0.18-1.3; P=0.131) and 0.18 (95% CI 0.04-0.84; p=0.029) respectively. The HR for PFS and OS for CHOP (n=14, reference) vs EPOCH (n=33) based regimens was 0.37 (95% CI 0.11-1.2; p=0.106) and 0.36 (95% CI 0.079-1.6; p=0.182) respectively. Patients with stage I/IE disease (n=56) had a 3-yr PFS and OS of 73.1% and 81.2% respectively. Patients with stage II/IIE disease (n=24) had a 3-yr PFS and OS of 69.3% and 73.4% respectively. Patients that received aggressive treatment (n=17) with Hyper-CVAD based regimens and/or Auto-SCT as consolidation had a 3-yr PFS and OS of 63.6% and 72.7% respectively. Patients with concomitant HIV (n=16) had a 3-yr PFS and OS of 80.8% and 77.4% respectively. Seven patients received RT alone and 6 patients had surgical resection alone as frontline therapy; 1 patient received no therapy; 1 patient received HAART therapy only and remains in CR without any other treatment for PBL 29 months after diagnosis. There were 8 deaths (10%) related to PBL, 3 deaths (4%) related to treatment of PBL (2 during frontline chemo and 1 upon relapse with salvage chemo), and 9 deaths (11%) related to other causes. The 3-yr lymphoma free survival (LFS) of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (without including treatment related mortality (TRM) as an event) was 89.1%, 85.2%, and 100% respectively. The 3-yr LFS survival of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (including TRM as an event) was 85.1%, 80.0%, and 96.2% respectively. Discussion: Here we report the largest review to our knowledge of limited stage PBL. Outcomes appear to be excellent with 3-yr PFS and OS of 71.9% and 78.7% respectively and a 3-yr LFS of 89.1% (85.1% when attributing TRM as an event). There was no obvious benefit to receiving aggressive therapy with H-CVAD based regimens and/or Auto-SCT. Although this is a small, uncontrolled sample size the HR for OS was improved in patients receiving frontline chemo-RT vs chemo alone 0.18 (95% CI 0.04-0.84; p=0.029). However, this did not take into account TRM with or progression while receiving frontline chemotherapy. Patients who were HIV+ had similar PFS and OS outcomes compared to the entire cohort. This retrospective study clearly demonstrates the favorable outcomes in this patient population, especially in those able to receive definitive therapy for their disease. Disclosures Hess: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Chavez:Bayer: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Verastem: Consultancy; Pfizer: Consultancy. Hill:Beigene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Maddocks:Pharmacyclics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; ADC Therapeutics: Consultancy, 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; Roche Laboratories Inc: Consultancy. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; OncLive: Honoraria. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Janssen Scientific: Consultancy, Other; Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; NCI: Research Funding. Portell:Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Takeda: Research Funding; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau. Castillo:TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding.
Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update
Loprinzi, Charles L. , Lacchetti, Christina , Bleeker, Jonathan , Chauhan, Cynthia, Hertz, Daniel L. , Kelley, Mark R. , Lavino, Antoinette, Lustberg, Maryam B. , Schneider, Bryan P. , Smith, Mary Lou , Wagner‐Johnston, Nina D. , Hertz, Daniel L , Lustberg, Maryam , Cavaletti, Guido , Paice, Judith A. , Lavoie Smith, Ellen M , Smith, Thomas J. , Hershman, Dawn L.

Journal of Clinical Oncology | July 14, 2020 | Volume: 38 | Issue: 28 | Pages: 3325-3348

10.1200/jco.20.01399 Get It

PURPOSE To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. RECOMMENDATIONS The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited. Additional information is available at www.asco.org/survivorship-guidelines .
Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial
Schöder, Heiko , Polley, Mei‐Yin C. , Knopp, Michael V. , Kostakoglu, Lale , Zhang, Jun , Higley, Howard R., Kelloff, Gary J. , Liu, Heshan , Zelenetz, Andrew D. , Cheson, Bruce D. , Wagner‐Johnston, Nina D. , Friedberg, Jonathan W. , Leonard, John P. , Schwartz, Lawrence H., Wilson, Wyndham H. , Bartlett, Nancy L. , Bartlett, Nancy L , Kostakoglu, Lale , Zelenetz, Andrew D , Schöder, Heiko , Hall, Nathan C. , Kahl, Brad S. , Hsi, Eric D.

Blood | March 31, 2020 | Volume: 135 | Issue: 25 | Pages: 2224-2234

10.1182/blood.2019003277 Get It

Abstract As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.
A Phase 2/3 Multicenter, Randomized Study Comparing the Efficacy and Safety of Lenalidomide Versus Investigator’s Choice in Relapsed/Refractory DLBCL
Czuczman, Myron S., Wagner‐Johnston, Nina D. , Gascoyne, Randy D. , Eberhard, David A., Staudt, Louis M. , Repici, Jacqueline, Song, Dale, Manzke, Oliver, Lewis, Ian D., Davies, Andrew , Linton, Kim , Salles, Gilles , Witzig, Thomas E. , Zinzani, Pier Luigi , Wright, George W.

Blood | October 11, 2019 | Volume: 124 | Issue: 21 | Pages: 628-628

10.1182/blood.v124.21.628.628 Get It

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin’s lymphoma (NHL) comprising 3 molecular subtypes: germinal center B-cell (GCB), activated B-cell (ABC) and class III. ABC patients (pts) have a poor prognosis. The immunomodulatory drug lenalidomide (Len) produces durable responses in pts with aggressive NHL (Witzig 2011), with preferential activity reported in non-GCB DLBCL (Hernandez-Ilizaliturri 2011). Methods: This randomized, multicenter, open-label, phase 2/3 study was conducted to determine the efficacy and safety of single-agent Len vs single-agent investigator’s choice (IC) in relapsed/refractory DLBCL pts who received ≥2 prior therapies, or were ineligible for stem cell transplantation or further combination chemotherapy. DLBCL subtype (GCB vs non-GCB) was determined by a central pathology lab using immunohistochemistry (IHC) per the Hans method (Hans 2004). Pts were stratified by subtype, then randomized 1:1 to receive Len (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin) until progressive disease (PD), unacceptable toxicity, or voluntary withdrawal. In the event of radiologically confirmed PD, pts in the IC arm were allowed to cross over to Len. The primary endpoint for Stage 1 was overall response rate (ORR), as determined by an Independent Response Assessment Committee. Progression-free survival (PFS), overall survival (OS) and subtype analysis using gene expression profiling (GEP) were exploratory endpoints. Concordance of GEP and IHC was evaluated from 3 separate laboratories. Results: IHC subtyping agreement rate among the 3 laboratories ranged from 87.5%-97.9%, and sensitivity of IHC to detect ABC or GCB subtypes vs GEP ranged from 92.3%-100.0%. By IHC, 102 DLBCL pts (GCB, n=48; non-GCB, n=54) were treated with ≥1 dose of Len or IC (modified intent-to-treat population) in Stage 1. In this heavily pretreated population, >90.0% of pts received ≥2 prior systemic chemotherapies; 25 pts in Len and 32 pts in IC received ≥3 prior systemic chemotherapy regimens. Median age was 65 y in the IC arm vs 69 y in the Len arm. Twenty-nine pts crossed over from IC to Len after confirmed PD. All pts, regardless of subtype or therapy group, experienced ≥1 treatment-emergent adverse event, with neutropenia, anemia, and thrombocytopenia being the most common. Efficacy data are presented in the Table. Pts with GCB or non-GCB DLBCL (per IHC) treated with Len had similar ORR, but the data suggested greater improvements in PFS and OS with Len vs IC in the non-GCB pts. In an exploratory analysis of pts subtyped by GEP, ABC pts treated with Len vs IC-treated showed greater improvements in ORR, PFS, and OS compared with GCB pts. Prespecified criterion to advance to Stage 2 was a 2-sided 15% significance level in ORR in favor of Len based on IHC-defined subtype. The data did not fulfill this requirement, and Stage 2 was not opened. Conclusion: Len monotherapy showed clinical activity in heavily pretreated pts with DLBCL. The data suggest improved ORR, PFS, and OS with Len vs IC in the non-GCB population as defined by IHC, and the difference appears to be more pronounced in the ABC population as defined by GEP. Subtyping by GEP is warranted in further studies of Len in DLBCL. Abstract 628. Table 1.Table. Efficacy DataBy IHCBy GEPOverallGCBNon-GCBGCBABCLen(n=51)IC(n=51)Len(n=23)IC(n=25)Len(n=28)IC(n=26)Len(n=14)IC(n=16)Len(n=11)IC(n=16)ORR, % (95% CI)27.5 (15.9-41.7)11.8 (4.4-23.9) 26.1 (10.2-48.4)12.0 (2.5-31.2)28.6 (13.2-48.7)11.5 (2.4-30.2)21.4 (4.7-50.8)12.5 (1.6-38.3)45.5 (16.7-76.6)18.8 (4.0-45.6)P Value .079 .279 .179 .642 .206PFS, med wk (95% CI)13.6 (8.6-17.7)7.9 (6.3-9.0) 10.1 (8.3-22.3)29.0 (6.3-20.6)15.1 (8.3-24.1)7.1 (5.3-8.4)13.2 (8.3-24.9)7.1 (6.0-20.6)82.0 (7.3-NA)6.2 (4.3-10.1)P Value .041 .550 .021 .506 .105HR (95% CI) 0.64 (0.41-0.99) 0.82 (0.43-1.57) 0.50 (0.27-0.92) 0.77 (0.35-1.68) 0.44 (0.15-1.23)OS, med wk (95% CI)31.0 (16.6-41.3)24.6 (12.7-33.9) 30.0 (14.9-44.4)24.9 (13.7-58.3)32.3 (15.9-48.1)20.4 (10.3-33.9)30.0 (18.0-34.6)20.1 (13.7-36.9)108.4 (9.6-108.4)18.6 (6.6-48.0)P Value .673 .526 .253 .767 .144HR (95% CI) 0.91 (0.59-1.41) 1.23 (0.65-2.34) 0.70 (0.38-1.30) 1.12 (0.52-2.42) 0.47 (0.17-1.33) Abbreviations: CI, confidence interval; HR, hazard ratio; med, median; NA, not applicable/not available. Disclosures Czuczman: Celgene: Consultancy. Off Label Use: This abstract describes a clinical trial of lenalidomide, which is an orally-available immunomodulatory agent under investigation for treating patients with diffuse large B-cell lymphoma.. Davies:GlaxoSmithKlein: Research Funding; Hoffman La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Wagner-Johnston:Celgene: Research Funding. Gascoyne:Celgene: Consultancy, Research Funding. Salles:Pfizer: Honoraria; Gilead: Honoraria; Jansen: Honoraria; Hoffman La Roche: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria. Witzig:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zinzani:Mundipharma: Honoraria; Pfizer: Honoraria; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Millennium Takeda: Honoraria; Celgene: Honoraria; Teva: Membership on an entity's Board of Directors or advisory committees. Wright:Celgene: Research Funding. Staudt:Celgene Corporation: Research Funding. Repici:Celgene: Employment. Song:Celgene: Employment. Manzke:Celgene: Employment.
Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high‐risk follicular lymphoma: CALGB 50904 (Alliance)
Blum, Kristie A. , Polley, Mei‐Yin C. , Dockter, Travis , Anderson, Sarah , Wagner‐Johnston, Nina D. , Christian, Beth , Atkins, Jim, Cheson, Bruce D. , Leonard, John P. , Bartlett, Nancy L. , Polley, Mei-Yin, Dockter, Travis J, Bartlett, Nancy L , Jung, Sin‐Ho , Hsi, Eric D.

Cancer | June 7, 2019 | Volume: 125 | Issue: 19 | Pages: 3378-3389

10.1002/cncr.32289 Get It

BackgroundThis multicenter, randomized phase 2 trial evaluated complete responses (CRs), efficacy, and safety with ofatumumab and bendamustine and with ofatumumab, bendamustine, and bortezomib in patients with untreated, high‐risk follicular lymphoma (FL).MethodsPatients with grade 1 to 3a FL and either a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2 with 1 lymph node >6 cm or an FLIPI score of 3 to 5 were randomized to arm A (ofatumumab, bendamustine, and maintenance ofatumumab) or to arm B (ofatumumab, bendamustine, bortezomib, and maintenance ofatumumab and bortezomib).ResultsOne hundred twenty‐eight patients (66 in arm A and 62 in arm B) received treatment. The median age was 61 years, and 61% had disease >6 cm; 29% had an FLIPI score of 2, and 71% had an FLIPI score of 3 to 5. In arm A, 86% completed induction, and 64% completed maintenance. In arm B, 66% and 52% completed induction and maintenance, respectively. Dose modifications were required in 65% and 89% in arms A and B, respectively. Clinically significant grade 3 to 4 toxicities included neutropenia (A, 36%; B, 31%), nausea/vomiting (A, 0%; B, 8%), diarrhea (A, 5%; B, 11%), and sensory neuropathy (A, 0%; B, 5%). The estimated CR rates were 62% (95% confidence interval [CI], 50%‐74%) and 60% (95% CI, 47%‐72%) in arms A and B, respectively (P = .68). With a median follow‐up of 3.3 years, the estimated 2‐year progression‐free survival (PFS) and overall survival (OS) rates were 80% and 97%, respectively, for arm A and 76% and 91%, respectively, for arm B.ConclusionsThe CR rates, PFS, and OS were not improved with the addition of bortezomib to ofatumumab and bendamustine in patients with high‐risk FL. Although grade 3 to 4 toxicities were similar, more patients treated with bortezomib required dose modifications and early discontinuation.
Clinical course of patients with cisplatin (CDDP)-associated neuropathy compared to other neurotoxic chemotherapy.
Albany, Costantine , Dockter, Travis , Wolfe, Eric, Pachman, Deirdre R. , Wagner‐Johnston, Nina D. , Lazzara, Kayla Marie, Sego, Lina M., Edwards, Sara I, Snow, C, Hanna, Nasser H. , Einhorn, Lawrence H. , Loprinzi, Charles L. , Costello, Brian A.

Journal of Clinical Oncology | May 28, 2019 | Volume: 37 | Issue: 15_suppl | Pages: e23078-e23078

10.1200/jco.2019.37.15_suppl.e23078 Get It

e23078 Background: There are limited patient (pt) reported outcome data regarding CDDP neurotoxicity. Methods: CDDP-induced peripheral neuropathy was evaluated in pts with testicular cancer planning to receive CDDP (20 mg/m2/d for 5 days) for ≥ 3 cycles. Neurotoxicity was assessed with the EORTC QLQ-CIPN20 tool before each CDDP cycle and every 2-4 months after, out to 18 months. We compared these data to our studies evaluating pts receiving doxorubicin/cyclophosphamide (AC), paclitaxel and oxaliplatin. The total score of the EORTC QLQ-CIPN20, each of the three subscale scores and each individual item was computed following the standard scoring algorithm and converted to a 0-100 scale. Descriptive statistics and graphical plots were utilized. Results: 54 pts receiving CDDP (mean age 33 years) and 18 pts receiving AC were evaluated. Following completion of CDDP, neuropathy symptoms (sensory neuropathy score and numbness/tingling in toes/feet) worsened for about 6 months (consistent with the so-called “coasting phenomena”), similar to what had previously been seen with oxaliplatin (but different than what had been seen with paclitaxel). For CDDP pts, during therapy, numbness and tingling in fingers/hands were more prominent, than the same symptoms in the toes/feet. After therapy was completed, numbness, and tingling became more prominent in toes/feet, but improved in the fingers/hands. After stopping therapy, shooting/burning pain did not worsen in upper or lower extremities. During therapy, CDDP pts had less problems than had previously been seen with oxaliplatin or paclitaxel, maybe because of the younger ages of the CDDP pts. With AC, all of the CIPN-20 sensory neuropathy scores were better than was seen in the pts receiving CDDP and also in pts receiving paclitaxel and oxaliplatin in previous evaluations. Conclusions: CDDP-induced neuropathy is more similar to oxaliplatin-induced neuropathy than paclitaxel-induced neuropathy. AC chemotherapy pts do not have substantial changes in CIPN 20 scores, consistent with the CIPN 20 instrument being a measure of chemotherapy-induced neuropathy, as opposed to more general chemotherapy-induced toxicities. Clinical trial information: NCT02677727.
A comparison of the natural history of oxaliplatin- and paclitaxel-induced neuropathy (NCCTG N08C1, N08CB/Alliance).
Ruddy, Kathryn J. , Pachman, Dierdre, Qin, Rui , Seisler, Drew K., Puttabasavaiah, Suneetha, Novotny, Paul J. , Ta, Lauren E., Beutler, Andreas S. , Wagner‐Johnston, Nina D. , Grothey, Axel, Dakhil, Shaker R. , Loprinzi, Charles L. , Lavoie Smith, Ellen M , Staff, Nathan P.

Journal of Clinical Oncology | April 19, 2019 | Volume: 33 | Issue: 15_suppl | Pages: 9564-9564

10.1200/jco.2015.33.15_suppl.9564 Get It

Venlafaxine to prevent oxaliplatin-induced neuropathy?: A pilot randomized placebo-controlled trial.
Zimmerman, Collin, Atherton, Pamela J. , Pachman, Deirdre R. , Seisler, Drew K., Wagner‐Johnston, Nina D. , Dakhil, Shaker R. , Lafky, Jacqueline M., Qin, Rui , Loprinzi, Charles L. , Grothey, Axel

Journal of Clinical Oncology | April 19, 2019 | Volume: 33 | Issue: 15_suppl | Pages: e20734-e20734

10.1200/jco.2015.33.15_suppl.e20734 Get It

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303
Bartlett, Nancy L. , Wilson, Wyndham H. , Pederson, Levi , Polley, Mei‐Yin C. , Pitcher, Brandelyn N., Cheson, Bruce D. , Friedberg, Jonathan W. , Staudt, Louis M. , Wagner‐Johnston, Nina D. , Blum, Kristie A. , Reddy, Nishitha , Chang, Julie , Chadburn, Amy , Mathew, Susan , Fisher, Richard I., Richards, Kristy L. , Leonard, John P. , Bartlett, Nancy L , Jung, Sin‐Ho , Hsi, Eric D. , Maurer, Matthew J. , Kahl, Brad S. , Abramson, Jeremy S. , Winter, Jane N. , Gopal, Ajay K. , Schöder, Heiko , Zelenetz, Andrew D.

Journal of Clinical Oncology | April 2, 2019 | Volume: 37 | Issue: 21 | Pages: 1790-1799

10.1200/jco.18.01994 Get It

PURPOSE Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma. PATIENTS AND METHODS Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety. RESULTS Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common ( P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm. CONCLUSION In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.
Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era
Gerson, James N. , Villa, Diego , Gerrie, Alina S. , Chapani, Parv , Medeiros, L. Jeffrey , Wang, Michael I., Cohen, Jonathon B. , Calzada, Oscar , Churnetski, Michael C. , Hill, Brian T. , Sawalha, Yazeed , Hernandez‐Ilizaliturri, Francisco J. , Kothari, Shalin , Bast, Martin, Fenske, Timothy S. , Gari, Swapna Narayana Rao, Maddocks, Kami J. , Bond, David A. , Bachanová, Veronika , Kolla, Bhaskar , Lansigan, Frederick , Donovan, Alexandra M., Wagner‐Johnston, Nina D. , Messmer, Marcus , Anderson, Jennifer K., Reddy, Nishitha , Kovach, Alexandra E. , Glenn, Martha, Inwards, David J. , Karmali, Reem , Kaplan, Jason , Rajguru, Saurabh, Evens, Andrew M. , Klein, Andreas K. , Umyarova, Elvira , Pulluri, Bhargavi , Amengual, Jennifer E. , Diefenbach, Catherine , Fisher, Richard I., Bachanova, Veronika , Sawalha, Yazeed , Gerrie, Alina S , Evens, Andrew M , Karmali, Reem , Bond, David A , Medeiros, L Jeffrey , Lansigan, Frederick , Diefenbach, Catherine S , Kovach, Alexandra E , Handorf, Elizabeth A. , Li, Shaoying , Vose, Julie M. , Chavez, Julio C , Shah, Bijal , Burns, Timothy Francis , Mehta, Amitkumar , Landsburg, Daniel J. , Caimi, Paolo F. , Lue, Jennifer Kimberly , Barta, Stefan K

Journal of Clinical Oncology | January 7, 2019 | Volume: 37 | Issue: 6 | Pages: 471-480

10.1200/jco.18.00690 Get It

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.