RARE DISEASE
Plasmablastic lymphoma
Plasmablastic lymphoma
Plasmablastic lymphoma
Synonyms: PBL
Synonyms: PBL
Synonyms: PBL
Drug discovery
1
drug
With orphan designation
Overview
Plasmablastic lymphoma (PBL) is a rare, aggressive CD20-negative large B-cell lymphoma associated with immunodeficiency (e.g., HIV, organ transplantation, or age-related immune decline). Characterized by plasmablastic morphology, high Ki-67 proliferation (often >90%), and frequent EBV association, it commonly presents with extranodal involvement (oral cavity, GI tract). Diagnosis requires immunohistochemistry showing plasma cell markers (CD138+) and lacks CD20 expression. Prognosis remains poor due to high relapse rates and chemoresistance.
Therapies
First-line: Intensive regimens (EPOCH, DA-EPOCH, hyper-CVAD) over CHOP due to better outcomes [5][6][9]
Novel agents: Bortezomib ± chemotherapy, lenalidomide, or checkpoint inhibitors (limited evidence) [5][9][12]
Adjunctive: ART for HIV-positive patients, CNS prophylaxis with intrathecal chemotherapy, autologous stem cell transplant in remission [1][5][6]
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
287 drug discovery papers about Plasmablastic lymphoma, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
287 drug discovery papers about Plasmablastic lymphoma, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | Aggressive Mandibular Plasmablastic Lymphoma in an HIV-Negative Patient: Clinicopathologic and Immunophenotypic Insights From a Rare Oral Case.
Plasmablastic lymphoma (PBL) is a rare and highly aggressive subtype of diffuse large B-cell lymphoma characterized by plasmacytic differentiation and a distinct immunophenotypic profile. It is most frequently associated with human immunodeficiency virus (HIV) infection and typically involves the oral cavity. However, PBL may also occur in immunocompetent individuals, representing a diagnostic and clinical challenge. This report describes a rare case of PBL affecting the mandible of an HIV-negative patient who presented with a rapidly progressive ulcerated oral lesion. Histopathological examination revealed a diffuse proliferation of large atypical cells with plasmablastic morphology and a high mitotic rate. Immunohistochemical analysis demonstrated strong expression of plasma cell markers, including CD138 and MUM1, along with negativity for conventional B-cell markers such as CD20 and CD79a. The Ki-67 proliferation index was approximately 90%, confirming the aggressive biological behavior of the neoplasm. Based on these findings, a diagnosis of PBL was established. Despite prompt referral for oncologic management and initiation of chemotherapy, the disease showed rapid progression with an unfavorable outcome. This case highlights the importance of including PBL in the differential diagnosis of aggressive oral lesions, even in HIV-negative and immunocompetent patients, and emphasizes the critical role of histopathological and immunohistochemical evaluation for accurate diagnosis.
2026-06-24 | Abstract A034: Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications
Abstract Background Plasmablastic lymphoma (PBL) and related Diffuse Large B-cell Lymphoma (DLBCL) variants with plasmablastic differentiation are aggressive malignancies characterized by high BCMA (TNFRSF17) expression, yet BCMA-targeted therapies remain largely unexplored in this setting despite poor outcomes with standard approaches. These tumors frequently present with extramedullary disease, poor vascularity, and profound immunosuppression – features that reduce the efficacy of Fc-dependent biologics and underscore the need for Fc-independent targeting approaches. Aim We aimed to identify small BCMA-binding peptide ligands (≈1–5 kDa) for theranostic applications in plasmablastic lymphomas. Our strategy focused on targeting the native BCMA receptor on intact tumor cells to preserve its physiological conformation, including its cysteine-rich ectodomain and membrane-associated lipid environment, which is critical for genuine epitope recognition and binding interactions. Methods We performed phage display screening to identify BCMA-binding peptides using large combinatorial peptide libraries displayed on M13 phage, through three iterative rounds of positive selection on BCMA-positive NCI-H929 cells and negative selection on induced BCMA-negative NCI-H929 cells. We subsequently performed in silico characterization of the binding mechanisms of selected peptides, including protein-peptide docking analyses using the HADDOCK server and binding free energy estimation with the PRODIGY tool. Results We identified three peptide scaffolds capable of binding BCMA in its native form on BCMA-positive cells. Peptide pBCMA_7 was selected because of its clonal prevalence and its binding affinity toward BCMA-positive tumor cells. Docking and free energy studies suggest a configuration in which the peptide associates with a surface-accessible region of BCMA, forming extensive interactions through both backbone and side-chain atoms. Molecular dynamics simulations further indicate a stable and consistent binding mode within an exposed pocket of the receptor. Notably, pBCMA_7 exhibited strong binding (-11.2 kcal/mol) across a range of plasmablastic lymphoma cell lines (DB, Pfeiffer, SU-DHL-2, U-2932, Karpas 422) as well as multiple myeloma cell lines (NCI-H929, U266 and IM9). Conclusion We report the identification of BCMA-binding peptide ligands with demonstrated activity in plasmablastic lymphomas and related large B-cell lymphomas with plasmablastic differentiation. These peptide scaffolds constitute a versatile theranostic toolkit supporting Fc-independent patient stratification, therapy monitoring and delivery of imaging and therapeutic agents. By establishing phage display against native receptors as a tractable strategy for ligand discovery in an unexplored oncological setting, this work opens a wide therapeutic space for BCMA-directed precision targeting in aggressive lymphomas. Citation Format: Elisabetta Pingitore, Khushboo Fatima, Selena Mimmi, Valentina Crapella, Anna Maria Zimbo, Antonio Lupia, Alessia Onali, Domenico Maisano, Francesco Bertoni, Alessandra Scagliola, Federica Melle, Maria Carmela Vegliante, Doriana Gramegna, Michele Guida, Sabino Ciavarella, Enrico Iaccino. Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A034.
2026-06-23 | Autologous Stem Cell Transplantation Of HIV-Positive Plasmablastic Lymphoma - Case Series.
Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) commonly associated with immunosuppressed conditions, such as HIV infection. Historically, HIV-positive patients were not considered candidates for aggressive systemic therapies due to the risk of life-threatening opportunistic infections. However, with the advent of highly active antiretroviral therapy (HAART), the management of HIV-associated lymphomas has improved, allowing for more intensive treatments, including autologous stem cell transplantation (ASCT). This case series explores the safety and efficacy of ASCT in HIV-positive patients with PBL as consolidation at first complete response (CR1) following first-line chemotherapy. Patients who underwent ASCT for PBL at CR1 after first-line chemotherapy were selected from the Bone Marrow Transplant (BMT) registry from January 2015 to December 2024. Clinical details, transplant specific details and outcomes were collected from the case records. Three cases of HIV-positive patients diagnosed with PBL underwent ASCT as consolidation therapy were included in the case series. ASCT was done after achieving complete metabolic response (CMR) following induction chemotherapy. All patients received dose-adjusted EPOCH chemotherapy along with HAART. HAART was temporarily withheld during conditioning chemotherapy. Prophylactic medications were administered to prevent infections. Complications during the peri-transplant period included febrile neutropenia and mucositis, but no opportunistic infections were reported. CD4 counts dropped during the transplant period but stabilized post-transplant, with no significant long-term decline. ASCT is a safe and effective treatment option for HIV-positive patients with PBL who achieve CMR after induction chemotherapy. The procedure is well-tolerated, with manageable complications and favourable long-term outcomes. ASCT should be considered as a consolidation therapy for eligible HIV-positive patients with PBL, offering the potential for prolonged disease-free survival.
2026-06-02 | Case Report: Synchronous Manifestations of Kaposi Sarcoma Herpesvirus-Associated Disorders.
Kaposi sarcoma herpes virus (KSHV) is associated with multiple clinical manifestations, including primary effusion lymphoma, an aggressive CD38+ B cell lymphoma with a plasmablastic phenotype. This case describes an antiretroviral therapy-adherent person with HIV who presented with concurrent KSHV-related disorders of Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and extracavitary primary effusion lymphoma (EC-PEL). Single-cell RNAseq (scRNAseq) and multiplex immunohistochemistry (mIHC) provide detailed insights into differences in cellular composition and viral and cellular transcriptomic differences between these diseases. Moreover, the case describes a long-term remission with single-agent anti-CD38 antibody, daratumumab, in a chemotherapy-refractory case. This case highlights the differing clinical manifestations of KSHV and the efficacy of immunotherapy in KSHV-associated primary effusion lymphoma.
2026-05-28 | Factors associated with treatment response and survival outcomes in plasmablastic lymphoma: A retrospective study in a predominantly Hispanic population.
e19099 Background: Plasmablastic lymphoma (PBL) is a rare, aggressive NHL with historically poor outcomes and a median overall survival (OS) of 9-15 months. We evaluated clinicopathologic characteristics and factors associated with response and survival in a predominantly Hispanic cohort of patients with PBL. Methods: We retrospectively analyzed 35 patients with pathologically confirmed PBL diagnosed between December 2012 and June 2025. Factors associated with response were assessed by chi-square and multivariable logistic regression. Survival outcomes were evaluated by Kaplan-Meier method with log-rank test and multivariable Cox regression. Results: Median age was 49 years; 85.7% were male, and 74.3% were Hispanic. Interim overall response rate (ORR) and complete response rate (CRR) with first-line therapy were 62.9% and 54.3%, respectively. On univariate analysis, female sex (p=.03) and LDH <220 U/L ( p <. 01) were associated with achieving CR. On multivariate analysis, LDH <220 U/L (OR .05, 95% CI .005–.54, p=.01) remained independently associated with CR after adjusting for ethnicity, age >40, ECOG >2, advanced stage, IPI ≥3, and Ki-67 >80%. With a median follow-up of 17 months, median progression-free survival (PFS) and OS were 20 and 60 months, respectively. Estimated 1-, 2-, and 5-year PFS were 59.3%, 49.2%, and 43.7%, and OS were 67.9%, 54.8%, and 46.0%, respectively. On univariate analysis, female sex (HR .29, 95% CI .09-.89, p=.03; HR .28, 95% CI .08-.96, p=.04) and achieving CR (HR .12, 95% CI .04-.34, p<.01; HR .11, 95% CI .04-.31, p<.01) were associated with improved PFS and OS. IPI ≥3 (HR 2.8, 95% CI 1.1-7.3, p=.03) and LDH ≥220 U/L (HR 2.7, 95% CI 1.0-6.9, p=.04) were associated with worse OS, but not PFS. On multivariate analysis, age >40 (HR 4.7, 95% CI 1.2-19.3, p=.03) was associated with worse PFS, but not OS. High/high-intermediate IPI scores (IPI ≥3; HR 7.4, 95% CI 1.2-47.1, p=.03; HR 12.7, 95% CI 1.4-118.6, p=.03) were independently associated with inferior PFS and OS, while achieving CR (HR .04, 95% CI .01-.38, p<.01; HR .03, 95% CI .003-.31, p<.01) was associated with improved PFS and OS, independent of LDH ≥220 U/L, interim response, disease stage, immunocompromised status, EBV status, CNS prophylaxis, radiation therapy, and autologous stem cell transplantation. Conclusions: In this predominantly Hispanic cohort, only half of patients achieved complete response following first-line therapy, with survival outcomes comparable to contemporary reports. Normal LDH at diagnosis was associated with higher CR rates, while high/high-intermediate IPI scores and failure to achieve CR after first-line therapy were associated with inferior survival. These findings underscore the need for more effective first-line treatment strategies to improve CR rates and long-term outcomes, particularly in patients with high-risk disease.
2026-07-11 | Aggressive Mandibular Plasmablastic Lymphoma in an HIV-Negative Patient: Clinicopathologic and Immunophenotypic Insights From a Rare Oral Case.
Plasmablastic lymphoma (PBL) is a rare and highly aggressive subtype of diffuse large B-cell lymphoma characterized by plasmacytic differentiation and a distinct immunophenotypic profile. It is most frequently associated with human immunodeficiency virus (HIV) infection and typically involves the oral cavity. However, PBL may also occur in immunocompetent individuals, representing a diagnostic and clinical challenge. This report describes a rare case of PBL affecting the mandible of an HIV-negative patient who presented with a rapidly progressive ulcerated oral lesion. Histopathological examination revealed a diffuse proliferation of large atypical cells with plasmablastic morphology and a high mitotic rate. Immunohistochemical analysis demonstrated strong expression of plasma cell markers, including CD138 and MUM1, along with negativity for conventional B-cell markers such as CD20 and CD79a. The Ki-67 proliferation index was approximately 90%, confirming the aggressive biological behavior of the neoplasm. Based on these findings, a diagnosis of PBL was established. Despite prompt referral for oncologic management and initiation of chemotherapy, the disease showed rapid progression with an unfavorable outcome. This case highlights the importance of including PBL in the differential diagnosis of aggressive oral lesions, even in HIV-negative and immunocompetent patients, and emphasizes the critical role of histopathological and immunohistochemical evaluation for accurate diagnosis.
2026-06-24 | Abstract A034: Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications
Abstract Background Plasmablastic lymphoma (PBL) and related Diffuse Large B-cell Lymphoma (DLBCL) variants with plasmablastic differentiation are aggressive malignancies characterized by high BCMA (TNFRSF17) expression, yet BCMA-targeted therapies remain largely unexplored in this setting despite poor outcomes with standard approaches. These tumors frequently present with extramedullary disease, poor vascularity, and profound immunosuppression – features that reduce the efficacy of Fc-dependent biologics and underscore the need for Fc-independent targeting approaches. Aim We aimed to identify small BCMA-binding peptide ligands (≈1–5 kDa) for theranostic applications in plasmablastic lymphomas. Our strategy focused on targeting the native BCMA receptor on intact tumor cells to preserve its physiological conformation, including its cysteine-rich ectodomain and membrane-associated lipid environment, which is critical for genuine epitope recognition and binding interactions. Methods We performed phage display screening to identify BCMA-binding peptides using large combinatorial peptide libraries displayed on M13 phage, through three iterative rounds of positive selection on BCMA-positive NCI-H929 cells and negative selection on induced BCMA-negative NCI-H929 cells. We subsequently performed in silico characterization of the binding mechanisms of selected peptides, including protein-peptide docking analyses using the HADDOCK server and binding free energy estimation with the PRODIGY tool. Results We identified three peptide scaffolds capable of binding BCMA in its native form on BCMA-positive cells. Peptide pBCMA_7 was selected because of its clonal prevalence and its binding affinity toward BCMA-positive tumor cells. Docking and free energy studies suggest a configuration in which the peptide associates with a surface-accessible region of BCMA, forming extensive interactions through both backbone and side-chain atoms. Molecular dynamics simulations further indicate a stable and consistent binding mode within an exposed pocket of the receptor. Notably, pBCMA_7 exhibited strong binding (-11.2 kcal/mol) across a range of plasmablastic lymphoma cell lines (DB, Pfeiffer, SU-DHL-2, U-2932, Karpas 422) as well as multiple myeloma cell lines (NCI-H929, U266 and IM9). Conclusion We report the identification of BCMA-binding peptide ligands with demonstrated activity in plasmablastic lymphomas and related large B-cell lymphomas with plasmablastic differentiation. These peptide scaffolds constitute a versatile theranostic toolkit supporting Fc-independent patient stratification, therapy monitoring and delivery of imaging and therapeutic agents. By establishing phage display against native receptors as a tractable strategy for ligand discovery in an unexplored oncological setting, this work opens a wide therapeutic space for BCMA-directed precision targeting in aggressive lymphomas. Citation Format: Elisabetta Pingitore, Khushboo Fatima, Selena Mimmi, Valentina Crapella, Anna Maria Zimbo, Antonio Lupia, Alessia Onali, Domenico Maisano, Francesco Bertoni, Alessandra Scagliola, Federica Melle, Maria Carmela Vegliante, Doriana Gramegna, Michele Guida, Sabino Ciavarella, Enrico Iaccino. Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A034.
2026-06-23 | Autologous Stem Cell Transplantation Of HIV-Positive Plasmablastic Lymphoma - Case Series.
Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) commonly associated with immunosuppressed conditions, such as HIV infection. Historically, HIV-positive patients were not considered candidates for aggressive systemic therapies due to the risk of life-threatening opportunistic infections. However, with the advent of highly active antiretroviral therapy (HAART), the management of HIV-associated lymphomas has improved, allowing for more intensive treatments, including autologous stem cell transplantation (ASCT). This case series explores the safety and efficacy of ASCT in HIV-positive patients with PBL as consolidation at first complete response (CR1) following first-line chemotherapy. Patients who underwent ASCT for PBL at CR1 after first-line chemotherapy were selected from the Bone Marrow Transplant (BMT) registry from January 2015 to December 2024. Clinical details, transplant specific details and outcomes were collected from the case records. Three cases of HIV-positive patients diagnosed with PBL underwent ASCT as consolidation therapy were included in the case series. ASCT was done after achieving complete metabolic response (CMR) following induction chemotherapy. All patients received dose-adjusted EPOCH chemotherapy along with HAART. HAART was temporarily withheld during conditioning chemotherapy. Prophylactic medications were administered to prevent infections. Complications during the peri-transplant period included febrile neutropenia and mucositis, but no opportunistic infections were reported. CD4 counts dropped during the transplant period but stabilized post-transplant, with no significant long-term decline. ASCT is a safe and effective treatment option for HIV-positive patients with PBL who achieve CMR after induction chemotherapy. The procedure is well-tolerated, with manageable complications and favourable long-term outcomes. ASCT should be considered as a consolidation therapy for eligible HIV-positive patients with PBL, offering the potential for prolonged disease-free survival.
2026-06-02 | Case Report: Synchronous Manifestations of Kaposi Sarcoma Herpesvirus-Associated Disorders.
Kaposi sarcoma herpes virus (KSHV) is associated with multiple clinical manifestations, including primary effusion lymphoma, an aggressive CD38+ B cell lymphoma with a plasmablastic phenotype. This case describes an antiretroviral therapy-adherent person with HIV who presented with concurrent KSHV-related disorders of Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and extracavitary primary effusion lymphoma (EC-PEL). Single-cell RNAseq (scRNAseq) and multiplex immunohistochemistry (mIHC) provide detailed insights into differences in cellular composition and viral and cellular transcriptomic differences between these diseases. Moreover, the case describes a long-term remission with single-agent anti-CD38 antibody, daratumumab, in a chemotherapy-refractory case. This case highlights the differing clinical manifestations of KSHV and the efficacy of immunotherapy in KSHV-associated primary effusion lymphoma.
2026-05-28 | Factors associated with treatment response and survival outcomes in plasmablastic lymphoma: A retrospective study in a predominantly Hispanic population.
e19099 Background: Plasmablastic lymphoma (PBL) is a rare, aggressive NHL with historically poor outcomes and a median overall survival (OS) of 9-15 months. We evaluated clinicopathologic characteristics and factors associated with response and survival in a predominantly Hispanic cohort of patients with PBL. Methods: We retrospectively analyzed 35 patients with pathologically confirmed PBL diagnosed between December 2012 and June 2025. Factors associated with response were assessed by chi-square and multivariable logistic regression. Survival outcomes were evaluated by Kaplan-Meier method with log-rank test and multivariable Cox regression. Results: Median age was 49 years; 85.7% were male, and 74.3% were Hispanic. Interim overall response rate (ORR) and complete response rate (CRR) with first-line therapy were 62.9% and 54.3%, respectively. On univariate analysis, female sex (p=.03) and LDH <220 U/L ( p <. 01) were associated with achieving CR. On multivariate analysis, LDH <220 U/L (OR .05, 95% CI .005–.54, p=.01) remained independently associated with CR after adjusting for ethnicity, age >40, ECOG >2, advanced stage, IPI ≥3, and Ki-67 >80%. With a median follow-up of 17 months, median progression-free survival (PFS) and OS were 20 and 60 months, respectively. Estimated 1-, 2-, and 5-year PFS were 59.3%, 49.2%, and 43.7%, and OS were 67.9%, 54.8%, and 46.0%, respectively. On univariate analysis, female sex (HR .29, 95% CI .09-.89, p=.03; HR .28, 95% CI .08-.96, p=.04) and achieving CR (HR .12, 95% CI .04-.34, p<.01; HR .11, 95% CI .04-.31, p<.01) were associated with improved PFS and OS. IPI ≥3 (HR 2.8, 95% CI 1.1-7.3, p=.03) and LDH ≥220 U/L (HR 2.7, 95% CI 1.0-6.9, p=.04) were associated with worse OS, but not PFS. On multivariate analysis, age >40 (HR 4.7, 95% CI 1.2-19.3, p=.03) was associated with worse PFS, but not OS. High/high-intermediate IPI scores (IPI ≥3; HR 7.4, 95% CI 1.2-47.1, p=.03; HR 12.7, 95% CI 1.4-118.6, p=.03) were independently associated with inferior PFS and OS, while achieving CR (HR .04, 95% CI .01-.38, p<.01; HR .03, 95% CI .003-.31, p<.01) was associated with improved PFS and OS, independent of LDH ≥220 U/L, interim response, disease stage, immunocompromised status, EBV status, CNS prophylaxis, radiation therapy, and autologous stem cell transplantation. Conclusions: In this predominantly Hispanic cohort, only half of patients achieved complete response following first-line therapy, with survival outcomes comparable to contemporary reports. Normal LDH at diagnosis was associated with higher CR rates, while high/high-intermediate IPI scores and failure to achieve CR after first-line therapy were associated with inferior survival. These findings underscore the need for more effective first-line treatment strategies to improve CR rates and long-term outcomes, particularly in patients with high-risk disease.
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Drug Discovery Landscape
1 orphan drug designation for Plasmablastic lymphoma.
1 orphan drug designation for Plasmablastic lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
nanatinostat and valganciclovir | small molecules | FDA | 2019-02-28 | — | Viracta Therapeutics, Inc. |
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