Porrata, Luis

ABSTRACT The recently published BLAST clinical risk model for chronic myelomonocytic leukemia (CMML) and its molecular version (BLAST‐Mol) differentiate low, intermediate, and high‐risk groups. The objective of the current retrospective study was to examine the survival impact of allogeneic stem cell transplant (ASCT) in a consecutive series of Mayo Clinic patients ( n = 775; 68% males, median age 71 years) with CMML, overall and adjusted for baseline BLAST/BLAST‐Mol risk categories. At a median follow‐up of 77 months, 151 (20%) patients underwent ASCT. Overall survival (OS) was longer in the ASCT compared to the non‐ASCT cohorts (median 77 vs. 28 months; p < 0.01). The significant difference in OS between the ASCT and non‐ASCT cohorts was retained after adjusting for BLAST clinical risk groups: high‐risk (median 50 vs. 14 months; p < 0.01), intermediate‐risk (81 vs. 28 months; p < 0.01), and low‐risk (111 vs. 65 months; p = 0.04), respectively. The same was mostly the case when OS comparison was adjusted for BLAST‐Mol with respective p values of < 0.01, < 0.01, and 0.08, respectively. Time‐dependent cox models confirmed the favorable survival impact of ASCT in the BLAST/BLAST‐Mol high‐ and intermediate‐risk groups. The current study highlights the benefit of ASCT for BLAST/BLAST‐Mol high‐ and intermediate‐risk groups in CMML and its potential to overcome the adverse impact of some high risk cytogenetic or molecular abnormalities. These observations support the early use of ASCT in CMML, ideally before BT and regardless of genetic characteristics.

Abstract Castleman disease (CD) is a heterogeneous group of lymphoproliferative disorders anatomically classified by distribution (unicentric CD [UCD], oligocentric CD [oligoCD], or multicentric CD [MCD]). Human herpes virus 8–negative MCD is called idiopathic MCD (iMCD), which includes clinical subtypes with varying phenotypes and responses: TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction and/or reticulin fibrosis, and organomegaly), IPL (idiopathic plasmacytic lymphadenopathy), and not otherwise specified. OligoCD has recently emerged as an intermediate form between UCD and MCD, with unclear clinical behavior, and IPL has not been validated in a Western cohort. We retrospectively analyzed 217 patients with CD evaluated at our institution between January 2004 and August 2024. Survival probabilities were compared using log-rank tests. Overall, 57% had UCD, 20% had oligoCD, and 23% had iMCD. Patients with oligoCD and iMCD more frequently exhibited systemic symptoms than those with UCD. Patients with oligoCD and iMCD had significantly shorter event-free survival (EFS) of 8.9 and 2.3 years, respectively, than those with UCD (not reached; P&lt; .001 and P&lt; .02). Among iMCD subtypes, iMCD-IPL demonstrated a longer EFS than iMCD-TAFRO (P = .02), with no deaths during the follow-up periods. The results validate oligoCD and iMCD-IPL as new subtypes in this Western cohort. The survival outcome in oligoCD was intermediate between UCD and iMCD, with only a subset of patients with oligoCD requiring systemic therapy. iMCD-IPL had a favorable survival outcome in this US cohort, similar to what has been reported in non-Western countries. Tailoring treatment strategies to disease subtypes and vigilant monitoring of oligoCD for progression may improve survival outcomes in CD.

Abstract Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma involving the brain, cerebrospinal fluid, or retina/vitreous without systemic involvement. Induction with high-dose methotrexate (HD-MTX) followed by consolidation with autologous stem cell transplant (auto-SCT) has become the standard treatment paradigm for most patients. However, limited data are available regarding the efficacy of a maintenance approach with HD-MTX. Herein, we retrospectively reviewed the characteristics and outcomes of 148 patients diagnosed with PCNSL between October 2010 and June 2022, who underwent HD-MTX–based induction therapy followed by either auto-SCT consolidation (n = 70) or HD-MTX maintenance therapy (n = 37). At a median follow-up time of 4.5 years, the progression-free survival (PFS) was 8.3 years and the overall survival (OS) was not reached. Compared to patients who underwent auto-SCT, patients who received maintenance HD-MTX had a higher median age at diagnosis of 72 vs 62 years and a trend toward higher proportion of patients being Eastern Cooperative Oncology Group 2 or higher (41% vs 29%). At 5-years postinduction treatment initiation, the PFS rates in the auto-SCT cohort and HD-MTX maintenance cohort were 74.6% and 72.6%, respectively, and the OS rates were 76.0% and 82.4%, respectively. Overall, there was no significant difference in PFS or OS based on postinduction management strategy. Our data suggest that maintenance HD-MTX may be a reasonable, time-limited treatment strategy for patients with PCNSL responding to initial induction therapy.

Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1–12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.

10088 Background: The ability of the immune system to recover its components after autologous stem cell transplantation (ASCT) is known to predict survival in patients with different types of neoplasms. Also, our previous work showed that polyclonal immunoglobulin can be used to improve T cell diversity and, consequently, T cell function in animal models. The aim of this retrospective study was to understand if the recovery of the polyclonal compartment of immunoglobulin in patients with multiple myeloma (MM) at day 100 (± 40d) after ASCT is a predictor factor for survival in MM patients who were subject to ASCT. Methods: From294 patients with IgG-MM subject to ASCT at the Mayo Clinic, Rochester, MN since October, 1993 until June, 2004, 143 patients were studied. The rational to select this group of patients was the fact that they had levels of serum IgM collected at day 100 ± 40 after ASCT recorded. Progression free survival (PFS) was assessed from the day of the transplant. PFS was studied using Kaplan-Meier curves and the univariate and multivariate analysis were done using age-adjusted proportional Cox. The prognostic variables in the multivariate model were: recovered of IgM at day 100, B2 microglobulin, age, conditioning regimen and disease status at the time of transplant. Results: There were 59 females in the study. The median age of the cohort was 58 y (33–75). The median follow up of the study was 26 mo (range, 2-111). PFS was significantly higher in the group who recovered normal serum levels of IgM at D100 compared to the pts who did not. This corresponds to a survival that is 1.5 longer in the group of patients who recovered normal levels of IgM at day100 after ASCT versus the patients who did not (median: 34 to 23 mo, respectively; p=0.05). By univariate analysis, those who did not recover normal serum levels polyclonal immunoglobulin by day 100 after ASCT had a risk of relapse 65% higher than the risk of the patients who recovered. Multivariate analysis suggests that recover the normal levels of polyclonal immunoglobulin after ASCT is an independent prognostic factor for PFS for MM patients after ASCT. Conclusions: These results suggest that polyclonal immunoglobulin is a major factor promoting immunity after ASCT. No significant financial relationships to disclose.

Abstract Introduction: The immunoglobulin (Ig) is one of the most diverse molecules in nature, and its therapeutic potential, by stimulation of the immune system, has been widely studied/used. Its effect is manifest at the cellular and humoral compartments. However it is still to clarify the specific effect of each fraction of the molecule in the observed immune stimulation. Aims: To develop a murine model of ASCT that mimics the autologous transplant in humans To study the independent effect of the various fractions of the immunoglobulin in the reconstitution of the immune system after ASCT. Methods: In this study, we developed, de novo, a murine model of ASCT. Four groups of transplanted animals were established (weekly injections of: Ig (n=8) or Fab fragment (n=7) or Fc fragment (n=6) or saline (control, n=7)). The evolution of the immune reconstitution was monitored weekly and compared among groups by characterization of cellular fractions by flow cytometry, serum levels of Igs by ELISA and thymic function by quantification of TRECs (“T cell receptor excision circles”). The statistical analysis of the longitudinal data was performed by a linear-mixed effects model. Results: We determined that a regimen of daily injections of G-CSF for 4 consecutive days produces a degree of mobilization of hematopoietic stem cells adequate for a donors/recipient ratio of 9 to 7, and to a standard engraftment extent. Regarding the recovery of cellular sub-populations among groups, the major differences occur up to the 6th week (w) after ASCT. As soon as 2 w after ASCT the treated groups show higher counts of CD4+ T cells compared with control mice (p<0.05). The maximum number of CD4+ T lymphocytes was attained at 2 w after ASCT for mice treated with Fab and Fc and at 9 w for mice treated with polyclonal Ig and PBS. The recovery of CD4+ T lymphocytes in the treated groups was higher compared to control (p<0.001 for Fab, p<0.001 for Fc and p=0.001 for polyclonal Ig). For CD8+ T cells, the mice treated with Fc show, during all the follow up, superior values, being statistically significant when compared to PBS treated mice (p=0.003). The differences with the other groups vary with time. Regarding the recovery of CD19+ lymphocytes, the mice treated with Fab reveal, after the 7th w, superior counts compared to all the other groups (p<0.05). Treated groups (Fab and Fc) show higher values of serum IgM compared to control, as well as an earlier recovery of levels (p<0.05). In what concerns CD4+ naïve T cells, the group treated with polyclonal Ig shows an increased recovery during the first weeks of treatment compared with the other groups (p<0.05). Conclusions and Discussion: The early treatment with polyclonal Ig or its fragments is highly beneficial for the recovery of CD4 and CD8 T lymphocytes (earlier recovery and higher cell counts). After the 6th week after transplant there is a tendency for homeostasis. The increase of CD4+ naïve T cells with Ig treatment may well correspond to an increased thymopoiesis, as suggested by our previous studies.

AbstractPatients with indolent non‐Hodgkin lymphoma (NHL) have multiple treatment options yet there is no consensus as to the best initial therapy. Lenalidomide, an immunomodulatory agent, has single agent activity in relapsed lymphoma. This trial was conducted to assess feasibility, efficacy, and safety of adding lenalidomide to rituximab, cyclophosphamide, and dexamethasone (LR‐CD) in untreated indolent NHL patients requiring therapy. This was a single institution phase II trial. Treatment consisted of IV rituximab 375 mg/m2 day 1; oral lenalidomide 20 mg days 1–21; cyclophosphamide 250 mg/m2 days 1, 8, and 15; and dexamethasone 40 mg days 1, 8, 15, and 22 of a 28‐day cycle. Treatment continued 2 cycles beyond best response for a maximum of 12 cycles without rituximab maintenance. Thirty‐three patients were treated. Median age was 68 (43–83 years). 39% had stage IV disease. Histologic subtypes included 8 follicular lymphoma (FL), 7 marginal zone lymphoma (MZL) (1 splenic, 2 extranodal, and 4 nodal), 15 Waldenström's macroglobulinemia (WM), 1 lymphoplasmacytic lymphoma, 1 small lymphocytic lymphoma, and 1 low‐grade B‐cell lymphoma with plasmacytic differentiation (unable to be classified better as MZL or LPL). Hematologic toxicity was the most common adverse event. Median time of follow‐up was 23.4 months (range 1.8–50.9). The overall response rate was 87.9%, with 30.3% complete response. The median duration of response was 38.7 months. The median progression free survival was 39.7 months, while median overall survival (OS) has not yet been reached. Lenalidomide can be safely added to a simple regimen of rituximab, oral cyclophosphamide, and dexamethasone and is an effective combination as initial therapy for low‐grade B‐cell NHL.