Abstract
Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1–196), the 3‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3‐year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper‐CVAD or auto‐SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.
1. INTRODUCTION
Plasmablastic lymphoma (PBL) is a rare subtype of non‐Hodgkin Lymphoma (NHL) first recognized as a distinct clinicopathologic disease entity in 1997 by the World Health Organization classification of lymphoid neoplasms. 1 Immunohistochemistry is consistent with a plasma cell phenotype with lack of expression of typical B‐cell markers, such as CD20. Both MYC translocations and EBV expression (i.e., Epstein–Barr virus encoded RNA, EBER) are commonly detected. 2 , 3 The clinical characteristics of patients diagnosed with PBL can be heterogenous. The diagnosis is commonly associated with immunocompromised states (e.g., human immunodeficiency virus [HIV], solid organ transplant patients) but occurs in immunocompetent patients as well. 3 , 4 , 5 Patients infected with HIV, as well as those who are immunocompetent, commonly have extranodal involvement at presentation with the most common sites of involvement the oral cavity/jaw and GI tract. 6 , 7
The clinical course of PBL is characterized by an aggressive course, high relapse rates after cytotoxic chemotherapy, and poor outcomes. 5 , 7 , 8 , 9 , 10 , 11 Mounting data have suggested that limited‐stage (LS) disease (Ann Arbor stage I‐II) may have a more favorable prognosis. 7 , 10 However, there has yet to be a dedicated review of LS patients and treatment recommendations from prior reviews have not commonly differentiated LS from extensive‐stage (ES) patients. Thus, many patients with LS disease are treated with aggressive therapy, such as auto‐SCT consolidation, based on the poor outcomes of PBL patients overall. 7 , 12 , 13 , 14 In addition, prognostic factors (i.e., HIV status, performance status, etc.) that affect outcomes of PBL patients in certain series have never been analyzed specifically in LS patients.
We describe the clinical characteristics, treatment patterns, and outcomes of LS PBL patients through a multi‐center retrospective analysis to provide insights into prognosis and support clinical decision making.
2. METHODS
Data on patients with LS PBL from 13 U.S. academic centers were collected. Institutional review board approval was obtained at each site and patients with a confirmed histologic diagnosis of PBL were eligible for inclusion. Determination of LS disease was determined by the Ann Arbor staging system. 15 Patients diagnosed with PBL between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcome data were extracted by retrospective chart review and included in a study‐specific data collection spreadsheet. Investigators at each center were responsible for assessing diagnostic criteria, stage, and response assessments as no central review related to pathology or imaging was performed. EBV expression of diagnostic tissue was reported as positive or negative without regard for utilization of a specific assay. Subsequently, individual centers were asked to qualify EBER expression performed on the diagnostic specimens as positive or negative if available. Responses were assessed by individual investigators utilizing institutional standard imaging modalities.
3. STATISTICAL ANALYSIS
Kaplan–Meier estimates were utilized for time to event analysis for overall survival (OS), progression free survival (PFS), and lymphoma free survival (LFS). The survival and survminer R packages were used to create and plot the survival curve from the Kaplan–Meier estimates. The 95% pointwise confidence interval band of the survival curves was obtained using the Greenwood's method. We also computed p‐values for log‐rank test for the difference of survival curves between groups. Cox proportional‐hazard regression models in the patients who received frontline chemotherapy were built with eight variables (Female vs. male, Age <60 vs. ≥60, HIV+ vs. HIV−, LDH < ULN vs. LDH ≥ ULN, Stage I/IE vs. Stage II/IIE, EBV+ vs. EBV negative in tissue biopsy, CHOP based frontline therapy vs. EPOCH based frontline therapy, and chemotherapy only vs. combined chemotherapy and radiation as frontline therapy). The univariate and multivariate regression results are reported as hazard ratio with 95% confidence interval. Specifically, a stepwise procedure was performed to fit the multivariate regression model. The significant predictors among eight variables were included in the regression model based on a significance level 0.15 for entry and for stay, which is a conservative approach. The reduced model was compared with a full model with all eight variables to see if adding variables lead to a significantly improved fit over the reduced model obtained from the stepwise procedure.
4. RESULTS
4.1. Patient characteristics
A total of 80 patients with LS PBL were identified. Baseline characteristics are included in Table 1. The median age was 58 years (range: 21–91); the male: female ratio was 4.7:1; and 20.5% (16/78) of the patient population were HIV positive. LDH was elevated in 23.6% (17/72) of the patients. Most patients (70.0%, or 56/80), were stage I or stage IE. Most patients, 82.5% (66/80), had extranodal involvement with the most common sites being sinus/nasopharynx 36.3% (29/80); GI tract 17.5% (14/80) including stomach, small intestine, and large intestine; along with 6.3% (5/80) occurring within the oral cavity, mandible, or tonsils (Table A1). Most patients (94.3%, or 66/70), had an ECOG PS of 0–2. Ki‐67 ≥ 80% was noted in 73.1% (38/52) of patients. EBV expression was defined as positive on tumor biopsy in 72.6% (53/73) of patients. Of the 44 tumor samples that were specifically evaluated for EBER by in situ hybridization, 77.3% (34/44) were positive and 22.7% (10/44) were negative.
TABLE 1.
Baseline characteristics
| Variable or Treatment | N (%) |
|---|---|
| Sex | 80 |
| Male | 66 (82.5) |
| Female | 14 (17.5) |
| Age | 80 |
| <60 | 38 (47.5) |
| ≥60 | 42 (52.5) |
| HIV | 78 |
| Positive | 16 (20.5) |
| Negative | 62 (79.5) |
| LDH | 72 |
| ≥ULN | 17 (23.6) |
| <ULN | 55 (76.4) |
| Stage | 80 |
| I | 4 (5) |
| IE | 52 (65) |
| II | 10 (12.5) |
| IIE | 14 (17.5) |
| Extranodal disease present | 66 (82.5) |
| Maxilla/sinus/nasopharynx | 29 (36.3) |
| Large intestine | 7 (8.8) |
| Oral cavity/mandible/tonsil | 5 (6.3) |
| Small intestine | 4 (5.0) |
| Other | 21 (26.3) |
| ECOG | 70 |
| 0–1 | 60 (85.7) |
| ≥2 | 10 (14.3) |
| Ki‐67 | 52 |
| ≥80% | 38 (73.1) |
| <80% | 14 (26.9) |
| EBV | 73 |
| Biopsy + | 53 (72.6) |
| Biopsy − | 20 (27.4) |
Abbreviation: ULN, upper limit of normal.
4.2. Patient treatment
Treatment characteristics are described in Table 2 and Figure 1. Of the 80 patients, 65 (81.3%) received frontline chemotherapy, of which 29 (36.3%) received frontline chemotherapy followed by consolidation with radiation therapy (RT), and 36 (45.0%) received frontline chemotherapy with no RT consolidation. Of the 65 patients that received frontline chemotherapy, 33 (50.8%) received EPOCH‐based (a combination of etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) treatment, 14 (21.5%) received a CHOP‐based (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, and 11 (16.9%) received aggressive Hyper‐CVAD (hyper‐fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) or modified Hyper‐CVAD‐like regimen. Of the 65 patients that received frontline chemotherapy, eight (12.3%) underwent Auto‐SCT consolidation. A minority of patients, 14 (21.5%), received bortezomib and 15 (23.1%) received rituximab as part of their frontline chemotherapy regimen. Data on CD20 expression for each diagnostic sample were not available. Of the 15 patients that did not receive frontline chemotherapy, seven (8.8%) received radiation therapy (RT) alone, six (7.5%) received surgical resection alone, one (1.3%) did not receive any therapy, and 1 (1.3%) was HIV+ and received anti‐retroviral therapy (ART) alone.
TABLE 2.
Treatment characteristics and patient outcomes
| Treatment characteristics | |
|---|---|
| Treatment | N (%) |
| Frontline chemotherapy | 65 (81.3) |
| EPOCH/R‐EPOCH | 21 (26.3) |
| CHOP/R‐CHOP | 12 (15.0) |
| V‐EPOCH | 12 (15.0) |
| Hyper‐CV/AD/Mod H‐CVAD | 11 (13.8) |
| V‐CHOP | 2 (2.5) |
| Other | 7 (8.8) |
| Radiation as frontline consolidation |
80 29 (36.3) |
| Transplant for consolidation | 80 |
| Consolidation with Auto SCT | 8 (10) |
| Outcomes | 80 |
| Alive | 60 (75.0) |
| Death related to PBL | 8 (10.0) |
| Death related to treatment | 3 (3.8) |
| Death (other) | 9 (11.3) |
| Patient outcomes | ||
|---|---|---|
| 3Y PFS (95% CI) | 3Y OS (95% CI) | |
| Entire Cohort (N = 80) | 72% (62, 83) | 79% (70, 89) |
| Outcomes by frontline therapy subgroup | ||
| Chemo + CRT (N = 29) | 85% (72, 100) | 96% (89, 100) |
| Chemo without CRT (N = 36) | 65% (50, 84) | 71% (56, 89) |
| CR to chemo + CRT (N = 27) | 87% (74, 100) | 96% (88, 100) |
| CR to chemo without CRT (N = 27) | 75% (59, 95) | 83% (69, 100) |
| EPOCH based frontline therapy (N = 33) | 77% (58, 100) | 90% (80, 100) |
| CHOP based frontline therapy (N = 14) | 62% (40, 95) | 84% (71, 98) |
| Hyper‐CVAD or modified Hyper‐CVAD (N = 11) | 64% (41, 99) | 73% (51, 100) |
| Chemo + Auto‐SCT consolidation (N = 8) | 63% (37, 100) | 63% (37, 100) |
| Chemo without Auto‐SCT consolidation (N = 57) | 72% (59, 87) | 81% (70, 94) |
| Radiation or Surgery alone as frontline treatment (N = 13) | 66% (43100) | 65% (41, 100) |
| Outcomes by clinical variable subgroup | ||
| Stage I/IE (N = 56) | 73% (62, 87) | 81% (71, 93) |
| Stage II/IIE (N = 24) | 69% (53, 91) | 73% (57, 94) |
| HIV positive (N = 16) | 81% (63, 100) | 77% (57, 100) |
| HIV negative (N = 62) | 69% (58, 83) | 78% (68, 90) |
| Lymphoma free survival (excluding death by TRM and death not attributed to PBL as an event) | ||
| Entire Cohort (N = 69) | ‐ | 86% (73, 93) |
| Chemo without CRT (N = 30) | ‐ | 84% (62, 93) |
| Chemo +CRT (N = 27) | ‐ | 96% (88, 100) |
| Lymphoma free survival (excluding only death not attributed to PBL as an event) | ||
| Entire Cohort (N = 72) | ‐ | 83% (78, 96) |
| Chemo without CRT (N = 33) | ‐ | 76% (71, 100) |
| Chemo +CRT (N = 27) | ‐ | 96% (88, 100) |
Abbreviations: 3Y PFS, three‐year progression free survival; 3Y OS, three‐year overall survival; Chemo, frontline chemotherapy; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CI, confidence interval; CR, complete remission to frontline chemotherapy; CRT, consolidative radiation therapy; EPOCH, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin; Hyper‐CVAD, hyper‐fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; OS, overall survival; PBL, Plasmablastic lymphoma; TRM, treatment related mortality; V, velcade (Bortezomib).
FIGURE 1.
Treatment flow chart. Auto‐SCT, autologous stem cell transplant. CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone. EPOCH, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. HAART, highly active antiretroviral therapy. Hyper‐CVAD, hyper‐fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone. PBL, plasmablastic lymphoma. RT, radiation therapy. [Color figure can be viewed at wileyonlinelibrary.com]
4.3. Patient outcomes and outcomes by frontline therapy
With a median follow up of 34 months (1–196), the 3‐year PFS and OS rates were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively (Figure 2A). Patient outcomes by frontline therapy are detailed in Table 2. The PFS and OS outcomes were investigated according to patients receiving frontline chemotherapy with consolidative RT versus frontline chemotherapy without consolidative RT (Figure 2B) as well as patients achieving a complete remission (CR) to frontline chemotherapy with consolidative RT versus patients achieving a CR who did not receive consolidative RT. Patients that received frontline chemotherapy with consolidative RT (N = 29) received a median of four cycles of chemotherapy (range 1–6), while patients who received frontline chemotherapy without RT consolidation received a median of six cycles of chemotherapy (range 1–6).
FIGURE 2.
Patient outcomes. (A) PFS and OS of entire cohort. (B) PFS and OS of patients receiving frontline chemotherapy alone versus frontline chemotherapy and radiation consolidation. (C) PFS and OS of patients receiving CHOP based frontline therapy, EPOCH based frontline therapy, and Hyper‐CVAD. based frontline therapy. (D) PFS and OS of patients with stage I/IE versus stage II/IIE. (E) PFS and OS of HIV (+) patients versus HIV (−) patients. CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; EPOCH, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin; OS, overall survival; PFS, progression free survival. [Color figure can be viewed at wileyonlinelibrary.com]
The patients that received chemotherapy and consolidative RT as frontline therapy had a hazard ratio (HR) of 0.61 (95% CI 0.19, 1.9, by univariate analysis) for PFS and 0.33 (95% CI, 0.064, 1.7) for OS, relative to patients receiving frontline chemotherapy alone. The hazard ratio reduction for progression by 39% (p‐value = 0.395) and death by 67% (p‐value = 0.189) were not statistically significant.
Outcomes based on frontline therapy were analyzed according to EPOCH‐based (N = 33) versus CHOP‐based (N = 14) versus Hyper‐CVAD based frontline therapy (N = 11) as well as patients that received Auto‐SCT consolidation (N = 8) versus no Auto‐SCT consolidation (N = 57) (Table 2; Figure 2C).
4.4. Relapse and survival
There was a total of twenty reported patient deaths (25%). Eight deaths (10%) were attributed to PBL, three deaths (4%) attributed to toxicity (one with frontline EPOCH, one with frontline Hyper‐CVAD, and one with salvage chemotherapy), and nine deaths (11%) related to other causes including sepsis not related to treatment (N = 1), secondary AML (N = 1), and not specified (N = 7).
The 3‐year LFS rates, excluding death by treatment related mortality (TRM) and death not attributed to PBL, for the entire cohort (N = 69), for patients that received frontline chemotherapy alone (n = 30), and for those receiving frontline chemo‐RT (N = 27) along with 3‐year LFS rates (including death by TRM as an event and excluding other causes of death not attributed to PBL) for the entire cohort (N = 72), for patients receiving frontline chemotherapy alone (N = 33), and for patients receiving frontline chemo‐RT (N = 27) were analyzed (Table 2).
Patients had PFS and OS outcomes investigated according to stage I/IE versus II/IIE (Figure 2D) and HIV+ status (Figure 2E). There were 13 patients that received either frontline RT alone or surgical resection alone with results reported in Table 2. One patient elected to proceed to hospice and passed away shortly after diagnosis with no therapy. One HIV positive patient with stage IE disease started on ART at diagnosis and achieved CR. This patient remained in CR at data submission, 29 months after diagnosis.
4.5. Prognostic factors
Among the eight variables evaluated, frontline chemotherapy regimen (EPOCH‐based vs. CHOP‐based) and LDH (≥ULN vs. <ULN) were considered to include in the multivariate model for PFS based on the significance level of 0.15 for entry and for stay. Both variables were significant with a significance level of 0.05 (Figure A1). Comparing the reduced model with frontline chemotherapy and LDH versus the full model with all eight variables, we fail to reject the reduced model (p‐value = 0.717) implying that additional six predictors were not helpful to improve the fit over the reduced model. Holding LDH constant, EPOCH‐based frontline chemotherapy reduced the PFS HR by a factor of 0.23 compared to CHOP (p = 0.029), and holding frontline chemotherapy constant, LDH ≥ ULN increased the PFS HR by a factor of 4.29 (p = 0.029). Univariate results showed in Table A2A,B for PFS and OS, respectively.
Among the eight variables, the use of EPOCH was the only variable selected by the stepwise procedure in the univariate analysis for OS. However, the p‐value was 0.182, which was not statistically significant. The additional seven variables did not improve the model fit over the EPOCH‐based chemotherapy only model (p‐value = 0.778).
5. DISCUSSION
Because of the low incidence of patients with LS PBL and corresponding lack of prospective trials, standard treatment guidelines are not clearly defined and rely on retrospective data. Due to the aggressive nature of the disease, high relapse rates, poor outcomes of PBL, and lack of reported outcomes for patients with limited stage disease, treatment recommendations generally favor aggressive regimens. Previous reviews of both LS and ES patients have shown a trend toward better outcomes with aggressive chemotherapy or consolidation with Auto‐SCT 13 , 14 while other reviews have not shown any clear benefit with more intensive regimens, 4 , 5 , 11 leaving clinicians with significant ambiguity in making treatment recommendations, especially in patients with LS disease. To the best of our knowledge, this is the largest review of LS PBL patients.
Herein, we describe overall favorable outcomes of LS PBL with three‐year PFS and OS probabilities of 72% (95% CI 62, 83) and 79% (95% CI 69, 89), respectively and a three‐year LFS probability of 83% (95% CI 73, 93) when censoring for death unrelated to PBL and 86% (95% CI 78, 96) when censoring for death unrelated to PBL and for death related to TRM.
In terms of clinical variables, there was no trend toward inferior PFS or OS in patients who were HIV+ at the time of diagnosis and seemed to be a trend toward improvement in PFS and OS in HIV+ patients in the multivariate analysis, although this was not statistically significant. Multivariate regression analysis showed a statistically significant increase in HR for PFS with elevated LDH at diagnosis when holding frontline chemotherapy constant and failed to add other clinical variables such as sex, age, stage, or EBV expression to the analysis to show any statistically significant effects on PFS or OS.
Caution should be used when interpreting the effect of different treatment variables on outcomes as this is a retrospective, non‐randomized comparison of different subgroups of a relatively small number of patients. In addition, the rationale behind each choice of treatment (e.g., choice of frontline chemotherapy, RT consolidation, etc.) for each patient is unknown. As well, this data set does not include the number of patients with PET‐CT scans and/or bone marrow biopsies at diagnosis, and it is possible some patients were more rigorously staged than others.
Patients that received aggressive frontline therapy, defined as Hyper‐CVAD or modified Hyper‐CVAD did not show improvement in PFS or OS compared to other frontline cytotoxic regimens such as CHOP‐ or EPOCH‐based therapy. Patients that received EPOCH‐based frontline therapy did show a trend towards improvement in PFS and OS compared to those that received CHOP‐based frontline therapy with multivariate regression analysis showing a statistically significant improvement in PFS with EPOCH‐based therapy when holding LDH constant. Any outcome improvement associated with EPOCH‐ versus CHOP‐based frontline therapy may be related to selection bias, with fitter patients being more likely to receive EPOCH‐based therapy. As well, patients treated with EPOCH‐based therapy may have been more often treated in an era with improved supportive care measures as compared to CHOP‐based therapy, perhaps affecting outcomes.
Patients that received RT consolidation after frontline therapy were associated with improvements in PFS and OS but neither was shown to be statistically significant in the multivariate regression analysis. This trend seemed to be consistent when analyzing patients that achieved a CR after receipt of frontline chemotherapy. However, data regarding disease location and disease bulk that could perhaps affect the decision for RT consolidation is not available.
In summary, this review demonstrates the favorable outcomes in PBL LS patients, especially in those able to receive definitive therapy for their disease. Aggressive frontline therapy with Hyper‐CVAD based regimens or auto‐SCT consolidation did not improve outcomes. Frontline therapy with EPOCH based regimens showed improved PFS outcomes versus CHOP based regimens that were statistically significant in multivariate regression analysis. Radiation consolidation after frontline chemotherapy was associated with improved outcomes over frontline chemotherapy alone, but these results did not meet statistical significance.
CONFLICT OF INTEREST
Brian T Hess: Advisory board for Bristol Myers Squibb and ADC Therapeutics; Anshu Giri: None reported; Yeonhee Park: None reported; Krina K Patel: Advisory board for Janssen, Bristol Myers Squibb, Pfizer, Merck, Cellectis, Precision Bio, Oncopeptides, Karyopharm. Research funding Bristol Myers Squibb, Janssen, Takeda, Allogene, Cellectis, Precision Bio, Nektar; Brian K Link: Consultancy with Genentech/Roche, MEI. Research funding Janssen, Genentech, Celgene, Genmab; Grzegorz S. Nowakowski: Research Funding Nanostrings, Celgene/Bristol Myers Squibb, Roche, MorphoSys. Consultancy Seattle Genetics, Curis, Ryvu, Kymera, Denovo, Kite, Celgene / Bristol Myers Squibb, Roche, MorphoSys; Seth M Maliske: Consultancy with Bristol Myers Squibb; Sonia Fortin: None reported; Julio C Chavez: None reported; Hayder Saeed: Advisory Board / Panel NCCN, Grant and Research Support Celgene Corporation, Janssen Pharma, Kite Pharma, MEI Pharm Inc, Nektar Therapeutics, TG Therapeutics. Consultancy Bristol‐Myers Squibb, Epizyme Inc., MorphoSys AG, Sanofi‐Aventis US, Seattle Genetics, Secura Bio Inc; Brian T. Hill: Consultancy, Honoria, and Research Funding Beigene, Abbvie, Genentech, Kite, Bristol Myers Squibb, Celgene, Pharmacyclics, Karyopharm. Honoraria Beigene, Abbvie, Genentech, AstraZenica, Kite, Bristol Myers Squibb. Research Funding Takeda. Consulting and Honoraria Novartis; Alex V Mejia Garcia: None reported; Kammi J Maddocks: Consultancy and Honoraria Pharmacyclics, Seattle Genetics, Morphosys, Celgene. Consultancy Karyopharm, ADC Therapeutics, AstraZeneca, Bristol Myers Squibb. Research Funding Bristol Myers Squibb; Walter Hanel: None reported; Nina D. Wagner‐Johnston: Advisory committees or membership on entity's board of directors ADC Therapeutics, Regeneron, CALIB‐R, Verastem; Marcus Raymond Messmer: None reported; Brad S. Kahl: Consultancy Genentech, ADC Therapeutics, Abbvie, AstraZeneca, BeiGene, Pharmacyclics, Celgene/BMS, TG Therapeutics, Hutchmed, MEI, MTEM, Kite, Epizyme, Takeda, Genmab, Incyte, Lilly. Research Funding Genentech, ADC Therapeutics, Abbvie, AstraZeneca, BeiGene; Marcus Watkins: None reported; Juan Pablo Alderuccio: Advisory board and received research support ADC Therapeutics. An immediate family member has served on the advisory boards of Puma Biotechnology, Inovio Pharmaceuticals, Agios Pharmaceuticals, Forma Therapeutics, and Foundation Medicine; Izidore S. Lossos: Advisory boards for Seattle Genetics, Janssen Scientific, Adaptive Biotechnologies, and Verastem; Sunita Nathan: None reported. Victor M; Orellana‐Noia: Advisory board ADC Therapeutics, Consultancy Genentech; Craig A. Portell: Consultancy: Bayer, Beigene, Kite, Amgen, Janssen, Pharmacyclics, Roche/Genetech. Research Funding Beigene, Kite, Acerta/AstraZeneca, AbbVie, TG Therapeutics, Infinity, Roche/Genetech, Xencor; Daniel J. Landsburg: Research Funding Triphase, Takeda, Curis. Consultancy Curis. Membership on an entity's Board of Directors or advisory committee Celgene, Curis, Karyopharm, Morphosys. Speakers Bureau Seattle Genetics; Emily C. Ayers: None reported; Jorge J. Castillo: Consultancy Abbvie, Beigene, Casma Therapeutics, Cellectar, Janssen, Pharmacyclics, Roche. Research funds Abbvie, AstraZeneca, Beigene, Pharmacyclics, TG Therapeutics.
APPENDIX A.
TABLE A1.
Extranodal disease subsites
| Extranodal disease present | 66 (82.5) |
| Maxilla/sinus/nasopharynx | 29 (36.3) |
| Large intestine | 7 (8.8) |
| Oral cavity/mandible/tonsil | 5 (6.3) |
| Small intestine | 4 (5.0) |
| Stomach | 3 (3.8) |
| Cutaneous | 2 (2.5) |
| Testicle | 2 (2.5) |
| Bone | 2 (2.5) |
| Spinal cord | 1 (1.3) |
| Bladder | 1 (1.3) |
| Breast | 1 (1.3) |
| Scrotum | 1 (1.3) |
| Not listed | 8 (10.0) |
TABLE A2.
Predictors of progression‐free survival and overall survival on univariate analysis
| (A) Progression‐free survival | |||
|---|---|---|---|
| Variable (N) | Univariate regression results | ||
| HR (CI) | p‐value | ||
| Sex |
Male (N = 66, Reference) Female (N = 14) |
1.23 (0.45, 3.29) | 0.677 |
| Age |
<60 (N = 42, Reference) ≥60 (N = 38) |
1.41 (0.65, 3.06) | 0.383 |
| HIV |
HIV negative (N = 62, Reference) HIV positive (N = 16) |
0.49 (0.15, 1.64) | 0.248 |
| LDH |
LDH < ULN (N = 55, Reference) LDH ≥ ULN (N = 18) |
1.78 (0.71, 4.44) | 0.218 |
| Stage |
Stage I/IE (N = 56, Reference) Stage II/IIE (N = 24) |
1.43 (0.64, 3.22) | 0.385 |
| EBV |
EBV negative (N = 20, Reference) EBV positive (N = 53) |
0.93 (0.38, 2.29) | 0.882 |
| Frontline |
CHOP (N = 14, Reference) EPOCH (N = 33) |
0.37 (0.11, 1.23) | 0.106 |
| Chemoradiotherapy |
Chemo only (N = 36, Reference) Chemo + RT (N = 29) |
0.46 (0.17, 1.24) | 0.126 |
| (B) Overall survival | |||
|---|---|---|---|
| Variable (N) | Univariate regression results | ||
| HR (CI) | p‐value | ||
| Sex |
Male (N = 66, Reference) Female (N = 14) |
1.35 (0.44, 4.08), | 0.598 |
| Age |
<60 (N = 42, Reference) ≥60 (N = 38) |
1.67 (0.67, 4.15), | 0.272 |
| HIV |
HIV negative (N = 62, Reference) HIV positive (N = 16) |
0.72 (0.21, 2.48), | 0.604 |
| LDH |
LDH < ULN (N = 55, Reference) LDH ≥ ULN (N = 18) |
1.14 (0.36, 3.58), | 0.823 |
| Stage |
Stage I/IE (N = 56, Reference) Stage II/IIE (N = 24) |
1.95 (0.78, 4.87), | 0.151 |
| EBV |
EBV negative (N = 20, Reference) EBV positive (N = 53) |
0.63 (0.24, 1.65), | 0.344 |
| Frontline |
CHOP (N = 14, Reference) EPOCH (N = 33) |
0.36 (0.08, 1.62), | 0.182 |
| Chemoradiotherapy |
Chemo only (N = 36, Reference) Chemo + RT (N = 29) |
0.18 (0.04, 0.84), | 0.029 |
FIGURE A1.
Predictors of progression‐free survival on multivariate regression analysis. ULN, upper limit of normal.
Hess BT, Giri A, Park Y, et al. Outcomes of patients with limited‐stage plasmablastic lymphoma: A multi‐institutional retrospective study. Am J Hematol. 2023;98(2):300‐308. doi: 10.1002/ajh.26784
Brian T. Hess and Anshu Giri contributed equally to this study.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.