Patients In Partial Remission Research Articles

Efficacy and safety of rechallenge [177Lu]Lu-PSMA-617 RLT after initial partial remission in patients with mCRPC: evaluation of a prospective registry (REALITY study).

Rechallenge of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) was proposed for patients who initially responded to PSMA-RLT experiencing partial remission, but relapsed into progression after a certain period of remission. However, only limited data is available regarding this approach. In this study, we analyzed the efficacy and safety profile of one or more series of [177Lu]Lu-PSMA-617 RLT rechallenge in patients from a prospective registry (REALITY Study, NCT04833517) after they initially benefited from PSMA-RLT. Forty-seven patients with metastatic castration-resistant prostate cancer (mCRPC) who had biochemical response to initial [177Lu]Lu-PSMA-617 RLT followed by disease progression received at least one (up to three) series of [177Lu]Lu-PSMA-617 RLT rechallenge. Biochemical response rates based on prostate-specific antigen (PSA) serum value, PSA-based progression-free survival (PFS) and overall survival (OS) were calculated. Adverse events of the treatment were assessed according to 'common terminology criteria for adverse events' (CTCAE). After one series of RLT rechallenge, a PSA decline of at least 50% was achieved in 27/47 patients (57.4%). The median PFS of all patients was 8.7 mo and the median OS was 22.7 mo, each calculated from the administration of the first rechallenge series. Patients who responded (PSA decline > 50%) to the rechallenge showed a median OS of 27.3 mo. Regarding PFS, a significant correlation (r = 0.4128, p = 0.0323) was found for these patients comparing initial and rechallenge RLT. Ten patients received a second and 3 patients received a third rechallenge series with 8/10 and 3/3 patients responding to repeated RLT rechallenge. No severe deterioration of adverse events rated by CTCAE criteria was observed. [177Lu]Lu-PSMA-617 RLT rechallenge is associated with significant PSA response and encouraging survival outcome as well as a very favourable safety profile and should therefore be considered as a straight-forward treatment option in mCRPC patients, who previously benefited from PSMA-RLT.

#2890 Role of alternative pathway of complement system in membranous nephropathy: a study from STARMEN clinical trials

Abstract Background and Aims Membranous nephropathy (MN) is an antibody-mediated autoimmune disease characterized by glomerular immune complexes containing complement components. A recent animal model of PLA2r antibody-induced MN induced has demonstrated the crucial role of complement pathway, although is still unclear which complement pathway is most involved in its pathogenesis This study aimed to explore the role of alternative pathway of complement cascade in a cohort of patients from STARMEN clinical trial. Method We analyzed longitudinal plasma samples from 51 patients from STARMENT cohort stored in a biobank. Samples were stored at enrollment and longitudinally throughout the follow up at 3, 6, 9, 12, 18 and 24 months. We measured the circulating plasma levels of C3, FB, FH, FHR1, FHR2 and FHR5 in every time. Results Fifty-two patients with a mean age of 56 ± 10 years and 60% male were included. 44% were treated with tacrolimus+Rituximab and 56% with ponticelli regimen. The basal creatinine was 0.9 ± 0.3 mg/dl, median proteinuria/day was 8.8 g/day (IQR 5.7-11.6 gr/day) and serum albumin of 2.6 g/dl (IQR 2.3-2.9 g/dl). All patients were followed-up for two years. Thirty-four patients achieved complete remission (CR), 11 patients partial remission (PR) and 15 did not respond (including relapse). During active disease, the mean concentration of FH, FHR-1 and FHR-2 were significantly increased compared with remission status (complete or partial). We did not find different in other factors: FB or FHR-5. Moreover, a positive correlation was observed between FH and FB with C3. There were no differences according to treatment arm. PLA2r antibodies tested positive in 68%. The median of baseline anti-PLA2R title levels was 80 RU/ml (IQR 43-141). Circulating plasma levels of FHR1 at baseline were significantly higher in PLA2r testing negative vs positive patients (199 ± 108 vs 249 ± 41 µg/ml, p = 0.021). This significant difference was present when remission was achieved (205 ± 97 vs 264 ± 49 µg/ml, p = 0.023). Similar tendency was observed for FB. Conclusion These data provide evidence of complement system activation through the alternative pathway in membranous nephropathy. We know that different subtypes of IgG are behind the different antibodies-induced MN induced, and that every subtype active different complement pathway. The results of this study lead to speculate that not all the antigens that induced MN active complement pathway in the same way.

Zanubrutinib Combined Regimen As Bridging Treatment on Promising Clinical Outcome of CD19 Chimeric Antigen Receptor T-Cell Therapies in Relapsed or Refractory Large B-Cell Lymphoma

Background Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) shows poor clinical outcomes. Anti-CD19 chimeric antigen receptor-T cells (CAR-T) therapy is emerging as the second-line therapy of choice, but in real-world studies its efficacy and long term follow is not promising. Effective bridging therapy can reduce tumor burden and improve CAR-T efficacy. Zanubrutinib, a selective Bruton tyrosine kinase (BTK) inhibitors, combined regimens have established therapeutic activity by targeting B-cell receptor signaling and have individually shown efficacy in patients with R/R DLBCL. Thus, the present study evaluated the efficacy and safety of zanubrutinib-combined regimen as bridging treatment in CD19 CAR-T therapy. Methods This retrospective study includes all patients participant in the clinical trail (NCT 02537977) between January 2020 and December 2022. All 21 heavily treated patients with r/r DLBCL who received zanubrutinib-combined regimens as bridging therapy are included. Patient clinical characteristics were collected upon patient enrollment. Efficacy outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), whereas safety outcomes included incidence of adverse events. The zanubrutinib combined regimens are zanubrutinib with IMIDs, chemotherapy and/or rituximab. Results: Of the 21 evaluable patients, median age of patients is 57 year old and median treatment line is 3. 19 patients (90%) are non-GCB subtype and 18 patients(86%) are IPI score >3. 14 patients(67%) are double expression and 7 patients (33%) have TP53 mutation. Objective response rate(ORR) is 81%; of whom, 10 patients(48%) got complete remission(CR) and 7 patients(33%) got partial remission(PR). With a median follow-up of 25 months, the median PFS was 12.8 months and median OS was not yet reached. 8 CR patients and 3 PR patients maintain long-term remission and are still under followup. 18 patients (86%) has grade 1-2 cytokines release syndrome(CRS) and 3 patients(14%) has grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). No severe CRS and >1 grade ICANS were observed. The most common hematologic toxicities included grade ≥3 neutropenia (90%) and grade 3/4 thrombocytopenia (71%). No patients had grade ≥3 non hematologic toxicities. Conclusion: Zanubrutinib-combined regimens are effective and safe as bridging therapy in CD19 CAR-T therapy. More prospective studies are further command.

The Prognostic Impact of Measurable Residual Disease Dynamics in Mantle Cell Lymphoma

Introduction Measurable residual disease (MRD) technologies have greatly enhanced our ability to guide treatment duration and predict outcome in various hematologic malignancies. However, drawing definitive conclusions on the benefits of achieving MRD-negative status in patients with mantle cell lymphoma (MCL) has been challenging due to the limited availability of large-scale MRD detection series. To address this, our study aimed to determine the optimal timing for MRD detection and explore the prognostic value of MRD dynamics in MCL. Methods In present study, we included 102 patients diagnosed with advanced MCL demonstrating clonal B cell involvement in bone marrow (BM) detectable by multiparametric flow cytometry (MFC). 60/102 (58.8%) patients received high dose cytarabine-based intensive immunochemotherapy. BM aspirates were collected and MRD assessment was conducted at specific time points, including the initiation of cycle 3, cycle 5, at the end of induction, and every 6 months during maintenance therapy. Results 77/102 (75.4%) patients reached MRD negativity throughout induction treatment. Of those with MRD − vs MRD + status , 23.4% vs 68.0% were aged >65 years respectively, which was likely a consequence of the greater MRD − rates observed in patients who received intensive immunochemotherapy and auto-transplantation. Besides, elevated lactate dehydrogenase (LDH) level, high-risk MIPI, blastoid/pleomorphic pathology type, and non-cytarabine containing regimen were associated with a lower rate of MRD negativity. Follow-up data revealed that MRD-negative patients had significantly better survival (P<0.001). In subgroup analyses, MRD negativity was prognostic in almost all subgroups. MRD detection serves as a valuable complement to the traditional response evaluation system, particularly benefiting patients who achieve partial remission (PR). This indicated the importance of assessing MRD during induction therapy for PR patients. However, for patients who achieve complete remission (CR), the presence or absence of MRD has minimal impact on prognosis (P=0.921 for progression-free survival (PFS), and P=0.399 for overall survival (OS). Then we evaluated the optimum timing of MRD detection and impact of rapidity of MRD negativity. 31 of the 77 patients (40.3%) had a rapid reduction of tumor burden and achieved MRD negativity after two cycles of treatment. 35 patients (45.5%) were MRD negative after four cycles of treatment. In 14.2% of the patients, MRD turned negative only at the evaluation after six cycles of induction therapy or during maintance duration. Comparing MRD status at different time points, the MRD status after four cycles of therapy was the strongest predictor of survival prognosis (HR=5.37, C-index=0.673). However, the speed of reaching MRD negativity was not significantly correlated with survival prognosis. Patients with high-risk features, such as high-risk MIPI, elevated LDH levels and complex karyotype, tend to achieve MRD negativity at a faster speed, often within two treatment cycles. However, faster rate of achieving MRD negativity did not confer any prognostic benefit to these patients. The overall MRD negativity rate was relatively low, and the prognosis for these patients was worse compared to other patients. In the high dose cytarabine-based intensive immunochemotherapy group, patients who achieved a rapid MRD negativity within two cycles of treatment showed a slightly longer PFS compared to those who achieved MRD negativity after 4-6 cycles (P=0.017). However, there was no significant difference in OS between the two groups. Conclusions In summary,the optimal timing for MRD testing is after four treatment cycles, as this time point demonstrated the best predictive ability for survival prognosis. However, the speed of achieving MRD negativity was not found to be linked with survival prognosis. Although certain high-risk features may lead to faster achievement of MRD negativity, this rapidity did not confer any additional prognostic benefit to these patients. Importantly, our results suggest that the value of MRD negativity as a prognostic marker may be limited in patients who have achieved complete remission and those with blastoid/pleomorphic morphologies. These findings underscore the need for tailored approaches to MRD testing and interpretation in MCL, in alignment with individual patient characteristics and treatment responses.

Influence of the occurrence and duration of partial remission on short-term metabolic control in type 1 diabetes: the DIABHONEY pediatric study.

To evaluate the residual effect of partial remission (PR) on immediate post-PR glycemic control according to its occurrence and duration in a cohort of children with type 1 diabetes mellitus (T1DM). Values of glycemic control parameters [i.e. HbA1C, insulin dose-adjusted hemoglobin A1C (IDAA1C), glycemic target-adjusted HbA1C (GTAA1C)] and data from glucose monitoring devices from 189 pediatric patients with new-onset type 1 diabetes were collected retrospectively from 24 months. Patients were characterized according to their remission status (PR+ and PR-). PR+ patients were subdivided into three subgroups regarding PR duration [i.e. short (⩾3-⩽6 months), intermediate (>6-⩽12 months), and long PR (>12-⩽14 months)]. We compared glycemic control data from each PR+ subgroup at +6 and +12 months post-PR with PR- patients at the same postdiagnosis time. Second, PR+ subgroups were compared with each other. PR+ patients showed improved glycemic control (i.e. HbA1C, IDAA1C, and GTAA1C) at + 6 months post-PR when compared with nonremitters (PR-), independently of the PR duration subgroups (p < 0.05). Interestingly, patients in long PR+ subgroup exhibited higher positive residual effect than short PR+ subgroup with lower GTAA1C scores (p = 0.02), better time in range (TIR) (p = 0.003), less time in hypoglycemia (10.45 versus 16.13%, p = 0.03) and less glycemic variability (83.1 mg/dl versus 98.84 mg/dl, p = 0.03). No significant differences were found for glucose control between PR+ and PR- patients at +12 months post-PR. This study supports the positive impact of PR occurrence and duration on short-term metabolic control (better HbA1C levels, IDAA1C and GTAA1C scores, TIR, and less glycemic variability) with the residual effect increasing according to PR duration.

Transcriptional and Genomic Characterization of Measurable Residual Disease (MRD) Cells in Acute Myeloid Leukemia (AML)

Background: Failure to achieve complete response (CR) and undetectable MRD is associated with inferior survival in AML. However, there is virtually no data on the molecular traits of treatment resistant cells to understand the mechanisms of MRD resistance. This would be particularly relevant in elderly AML, for which outcomes remain dismal despite increasing CR rates with novel combinations. Aim: Uncover mechanisms of MRD resistance in elderly AML by comparing the transcriptional and genomic profile of patient-matched leukemic cells at diagnosis and after treatment with semi-intensive chemotherapy or hypomethylating agents. Methods: 285 AML patients with a median age of 75 were included in the phase 3 PETHEMA-FLUGAZA trial and were randomized to receive induction and consolidation with fludarabine and cytarabine (FLUGA) vs 5-azacitidine (AZA). After consolidation, patients continued with the same treatment if MRD ≥ 0.01% or stopped if MRD < 0.01%. MRD was assessed using multidimensional flow cytometry, and highly-purified MRD cells were isolated according to patient-specific aberrant phenotypes using FACS. Leukemic blasts and T cells (germline control) were also sorted at diagnosis. A 3' end RNAseq method optimized for generating libraries from low-input starting material (MARSeq) was used. RNAseq was performed at diagnosis in 220 patients, and in paired diagnostic-MRD leukemic cells from 22 patients. Whole-exome sequencing (WES) was performed using molecular barcoding in paired diagnostic-MRD leukemic cells from 14 patients. Results: After induction, 35 patients were in partial remission (PR), 51 attained CR/CRi but persistent MRD (CR/MRD+), and 13 achieved CR/CRi and undetectable MRD (CR/MRD-). There were no differences in median overall survival (OS) between patients in PR vs CR/MRD+ (median of 21 vs 20 months, p = .603), and both were numerically inferior to that observed in CR/MRD- patients (median of 27 months, p = .097). There was only one gene (PIEZO2) differentially expressed between leukemic cells at diagnosis vs after treatment in patients achieving PR (n = 10). By contrast, there were 117 differentially expressed genes between leukemic cells at diagnosis vs after treatment in CR/MRD+ patients (n = 12). To confirm that gene deregulation was intrinsically associated with treatment resistance, the prognostic value of gene (over or under) expression in accordance with the differential observed between diagnostic and MRD leukemic cells, was subsequently analyzed in the 220 patients with RNAseq data at diagnosis. Over expression of 3 genes (IGFBP2, LINC00475 and PLEKHG3) and under expression of 12 genes (eg, CASC15, KDM7A and MEX3B) among the 117 identified above, was significantly associated with inferior OS. Interestingly, none of the genes was prognostic in the BeatAML cohort, suggesting that the transcriptome of MRD resistance may be specific of treatment. A total of 6,054 mutations were detected after WES of matched leukemic cells at diagnosis and after treatment, in 14 patients achieving CR/MRD+. Amongst these, 4,708 (78%) were detected at both time points, 354 (6%) were present at diagnosis while absent in MRD blasts, and 992 (16%) emerged during MRD resistance (p ≤ 0.008). There were no differences between treatment arms in the number of shared and private mutations in diagnostic vs MRD cells. Amongst the 1,346 mutations that either became undetectable or present at MRD, recurrence (ie, ≥ 3 patients) was observed in 47 genes. Acquired mutations in AVP and UBXN11 were observed in MRD cells from 6 of the 14 patients. Conclusions: This study showed that elderly AML patients treated with semi-intensive chemotherapy or hypomethylating agents, have dire survival regardless of achieving PR vs CR/MRD+. However, RNAseq analyses of resistant cells uncovered that whereas PR is characterized by primary resistance and transcriptionally stability from diagnosis, CR/MRD+ is associated with the emergence of molecular traits of acquired resistance. These findings could help explaining why additional treatment with the same schema is unable to overcome the poor prognosis of persistent MRD in elderly AML patients achieving CR/CRi. First-ever simultaneous RNAseq and WES of patient-matched diagnostic and MRD blasts, suggests that a few deregulated genes and recurrent mutations with limited or previously unknown role in AML pathobiology, are associated with MRD resistance and inferior OS.

IBCL-409 The Expediency of Early Administration of Second-Line Therapy to Patients in Partial Remission of Follicular Lymphoma

The overall survival (OS) of follicular lymphoma (FL) patients in complete remission (CR) exceeds that in partial remission (PR). To achieve CR in PR patients, second-line therapy (SLT) may be carried out immediately, or in disease progression after supportive rituximab treatment. To determine the early SLT feasibility. We conducted retrospective comparative analysis of two patient groups in the PR after R-CHOP. Group No.1 received SLT immediately early after first-line therapy (FLT) completion, and group No.2 received maintenance rituximab with SLT inly in case of disease progression. The study included 55 FL patients. R-CHOP program was used as FLT, and the R-DHAP program (rituximab, dexamethasone, cytarabine, cisplatin) was used as the SLT. Group No.1 included 22 PR patients who were allowed for rituximab maintenance and R-DHAP treatment in case of disease progression. Group No.2 consisted of 33 PR patients who received R-DHAP as SLT immediately after FLT completion. Disease progression on rituximab maintenance was detected in four patients in group No.1 (18%). Progression occurred early after FLT, 7 months median (4-24 months). R-DHAP as SLT led to CR in one patient (25%, in 7 months he had refractory relapse and died). In three patients (75%,) FL progressed after R-DHAP (two died in progression and one is alive on multiple other courses). Eighteen of 22 patients (82%) remain in the PR and do not need SLT. The 7-year OS was 73% and event free survival (EFS), 70%. In No.2 group R-CHOP+R-DHAP therapy led to additional CR in 26 cases (79%), PR was preserved in six (18%) and resistance was observed in one patient. Subsequently, two relapses and five progressions developed in seven patients (21%) with 7 months median (4-58 months). The 7-year OS was 82% and EFS - 66%. There was no difference in OS and EFS between No.1 and No.2 groups in Log-Rank Test (p=0.6 and p=0.77, respectively). Our results showed that in cases of PR FL achievement, observation may be chosen, since the early R-DHAP appointment after FLT has no advantages over the later initiation in case of disease progression.

PB1941: PRELIMINARY EXPLORATION OF PROLONGED USE OF ELTROMBOPAG IN PATIENTS WITH NAÏVE SEVERE APLASTIC ANEMIA IN THE REAL WORLD: DURATION AND EFFICACY

Background: Eltrombopag (E-PAG) plus the immunosuppressive therapy (IST) consisted by antithymocyte immunoglobulin (ATG) and cyclosporin (CsA) has been reported with better efficacy in both refractory and naïve severe aplastic anemia (SAA) patients than IST alone. E-PAG was used up to 6 months in clinical trials. Patients with refractory SAA who remained on E-PAG with a median duration of 12 months showed further hematological improvement. Aims: To explore whether patients with naïve SAA could benefit from continuous use of E-PAG beyond 6 months and when E-PAG should be withdrawn in patients with no response. Methods: From February 2018 to November 2021, we collected 57 Chinese adult patients with naïve SAA who were treated with rabbit-ATG based IST (r-ATG, 3.5mg/kg/d × 5d and CsA 3-5 mg/kg/d) combining with E-PAG at dose of 75mg per day in the China Eastern Cooperation Group for Anemia (Clinical trials: ChiCTR2100045895). All patients were treated with E-PAG at least 6 months, and then whether to continue treatment was decided by the attending doctor according to patients’ situation. The dosage of E-PAG would be tapered gradually at 3 months after complete remission (CR) or 6 months after stable partial remission (PR). Results: Clinical and laboratory characteristics of patients were listed in Table 1. The median time from diagnosis to treatment was 3 weeks (1 week to 291 weeks). The median follow-up time was 17 months (1 month to 44 months) and overall survival rate was 98%. The overall response rates were 35% (20 of 57), 67% (36 of 54), 84% (42 of 50) and 95% (41 of 43) at 1, 3, 6 and 12 months, and CR rates were 17% (9 of 54), 24% (12 of 50) and 35% (15 of 43) at 3, 6 and 12 months. The first response was observed at 2 weeks after treatment, and the median time to remission during the first 6 months was 11 weeks (2 weeks to 25 weeks). 11% of patients achieved efficacy between 7 and 12 months. In patients with NR after continuous use of E-PAG for 12 months, no more patients met criteria for PR by extending the treatment of E-PAG. The cumulative effect curve showed that 88 percent of all 12 months responses occurred within 6 months, and the efficacy reached a peak at 6 months (Figure 1). 11 patients (22%, 11 of 50) who achieved CR within 6 months were under steady state with the exception of 1 patient converting to paroxysmal nocturnal hemoglobinuria at 12 months after treatment. In 30 patients achieved PR at 6 months, 5 patients (17%, 5 of 30) discontinued E-PAG after 6 months and 25 patients had a continuous exposure to E-PAG, while the efficacy of 13 patients (52%, 13 of 25) were improved to CR within median extended usage time of 9 months (2 to 31 months) of E-PAG, and the dose of E-PAG was tapered gradually in 6 patients (24%, 6 of 25), maintained at 75mg per day in 7 patients (28%, 7 of 25). The other 12 patients (48%, 12 of 25) were in stable PR. In 8 patients (16%, 8 of 50) were ineffective at 6 months, 1 patient died early at 1 month; 2 patients achieved PR at 12 months by E-PAG continuously; 5 patients treated with CsA alone latter; and 2 patients achieved CR at 12 months, 3 patients still were in NR in CsA alone group. Image:Summary/Conclusion: It was suggested that E-PAG was used at least 6 months. Continuous administration of E-PAG could improve the hematological response of PR patients to CR. No patient with NR taking effect after 12 months, new options should be considered with caution for them.

Achievement of clinical-laboratory and ASAS-partial remission in patients with early axial spondyloarthritis according to the ESAC cohort at the 3rd year of follow-up

According to the treat-to-target strategy for spondyloarthritis (SpA), the main goal is to achieve clinical remission or inactive disease. In 2001, the Assessment of Spondyloarhtritis International Society (ASAS) formulated the ASAS criteria for partial remission, and the Russian expert group for the study of SpA identified clinical-laboratory remission (no clinical manifestations of the disease that persists for 6 months in the presence of normal values of C-reactive protein and erythrocyte sedimentation rate), magnetic resonance imaging (MRI) remission and complete remission (a combination of clinical-laboratory and MRI remission). To determine the frequency of achieving clinical-laboratory and ASAS partial remission in patients with early axial SpA (axSpA) at the 3rd year of follow-up. The study included patients from the ESAC cohort (Early SpondyloArthritis Cohort), formed at the Nasonova Research Institute of Rheumatology (Moscow). Currently, the cohort includes 175 patients with axSpA. The analysis included 66 patients followed for at least 3 years, of which 37 (56%) were men and 29 (44%) were women. The average age of the patients was 31.5 (5.7) years, the average duration of the disease was 22.1 (17.0) months, 63 (95.4%) patients had HLA-B27 antigen. Clinical-laboratory remission was achieved by 21 (31.8%) patients with early axSpA at the 3rd year of follow-up, ASAS partial remission by 29 (44.0%) patients. In the 3rd year of follow-up of patients with early axSpA, 32% of patients achieved clinical-laboratory remission, and 44% of patients achieved ASAS partial remission. More than 40% of patients with early axial spondyloarthritis achieve remission while taking non-steroidal anti-inflammatory drugs.

Clinical characteristics of multicentric reticulohistiocytosis and distinguished features from rheumatoid arthritis: a single-center experience in China

ObjectiveTo investigate the clinical features of multicentric reticulohistiocytosis (MRH).MethodsThe clinical manifestations, laboratory examination results and histologic characteristics of eleven patients with MRH were collected and compared with those of 33 patients with rheumatoid arthritis.ResultsIn total, 72.7% of the MRH patients were women. The median age was 46 years (range 33–84 years). Diagnosed by specific pathologic features, all MRH patients exhibited cutaneous involvement. The dorsa of the hands, arms, face and auricle were the most commonly affected areas. Nodules were also located on the legs, scalp, trunk, neck, and even the hypoglossis and buccal mucosa. Ten MRH patients (90.9%) had symmetric polyarthritis. Compared with rheumatoid arthritis (RA) patients, MRH patients were more likely to have distal interphalangeal joint (DIP) involvement (63.6% vs 24.2%, P = 0.017) and less likely to have elbow (36.4% vs 72.7%, P = 0.003), ankle (45.5% vs 93.9%, P < 0.001) and metacarpophalangeal joint (MCP) (36.4% vs 78.8%, P = 0.009) involvement. Positivity for rheumatoid factor (RF) (36.4% vs 84.6%, P = 0.001) and anti-CCP antibody (9.1% vs 81.8%, P = 0.000), as well as the median RF titer [43.8 (31.7–61.0) vs 175.4 (21.3–940.3), P = 0.021], in MRH patients was lower than in RA patients. Elevation of the erythrocyte sedimentation rate (ESR) was also less common in MRH patients than in RA patients (36.4% vs 72.7%, P = 0.030). After treatment with median- to large-dose corticosteroids and disease-modifying antirheumatic drugs, 8 patients achieved complete remission and 2 patients partial remission (skin lesions ameliorated, joint lesions not ameliorated).ConclusionAlways pathologically diagnosed, MRH is a systemic disease involving RA-like erosive polyarthritis and a specific distribution of skin nodules characterized by "coral beads". More DIP involvement and less elbow, ankle and MCP involvement are seen in MRH than in RA. In addition, less positivity and lower-titer RF, uncommon presence of anti-CCP antibodies and ESR elevation may be helpful to distinguish MRH from RA.

A prospective observational study on efficacy of modified rheumatoid arthritis protocol of rituximab (2000 mg) on patients of pemphigus

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Rituximab (RTX), an anticluster of differentiation 20 antibody, targets B lymphocytes, has been shown in open series studies to be effective in treating pemphigus. The objective was to evaluate whether a modified rheumatoid arthritis protocol, in which the patient received four doses of 500 mg of rituximab at an interval of two weeks was safe and effective in pemphigus management.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; It was a prospective observational study in which 46 pemphigus patients included and four doses of 500 mg of RTX at an interval of two weeks given and number of doses required for complete remission (CR), proportion of patient respond partially or doesn’t respond or relapsed after CR.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; We enrolled 46 patients in the study, 8 with pemphigus foliaceus (PF) and 38 with pemphigus vulgaris (PV). 20 were male and 26 were female followed up for 15±4.24 months (12-18). All patient responded to therapy. CR of 23 patient after 2 dose OF 500 mg RTX ,of 18 patient after 3 dose, 5 patient partial remission (PR) after 4 doses. All patient were on 100 mg OD azathioprine. PR, all have oral lesions got CR after 3 weeks of 4th dose. 3 patients relapsed MD 11±2.8 months (9-13 months) and given additional dose of 500 mg RTX and got resolved in 3 weeks.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; We found modified rheumatic arthritis protocol for RTX was shown to be effective in treatment of pemphigus patient and relapse cases with additional dose. Immunological assay were not performed to limit the study.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Undetectable minimal residual disease is an independent prognostic factor in splenic marginal zone lymphoma.

The role of minimal residual disease (MRD) in splenic marginal zone lymphoma (SMZL) has not been well studied. We prospectively designed a study to evaluate undetectable MRD (uMRD) by multiparameter flow cytometry as a prognostic factor. Residual disease level of <0·01% was defined as uMRD. A total of 71 newly diagnosed patients with bone marrow involvement were enrolled and all received rituximab-based therapy. The overall response rate (ORR) was 98·5% (70/71), with a complete remission (CR) rate of 54·9% (39/71). There were a total of 295 MRD detections in bone marrow and 77·4% patients (55/71) had uMRD. The 5-year progression-free survival (PFS) [(74·8±6·5)% vs. (31·4±12·6)%, P<0·001] and 5-year overall survival (OS) [(87·2±5·6)% vs. (68·9±13·4)%, P=0·035] were significantly higher in uMRD patients than in MRD-positive patients. The 5-year PFS in partial remission (PR) patients with positive MRD was significantly poorer than that of PR patients with uMRD [(21·1±12·9)% vs. (83·3±8·8)%, P=0·005]. Multivariate prognostic analysis revealed that uMRD was an independent good prognostic factor for PFS (hazard ratio 0·162, 95% confidence interval 0·041-0·635; P=0·009). All these results highlight uMRD as an independent prognostic factor in patients with SMZL, especially for patients who only achieve PR.

Disease Status at Transplant has a Significant Impact on Outcomes of Autologous Transplantation (ASCT) in Patients with Hodgkin Lymphoma-A Single Center Experience.

High dose chemotherapy followed by autologous stem cell transplantation is the treatment of choice for relapsed Hodgkin lymphoma (HL). We analyzed 100 consecutive patients who underwent ASCT at our center between January 1999 and June 2019 for relapsed or refractory disease with a median age of 28years (range: 9-65). At ASCT, 59 were in complete remission (CR) while 31 achieved partial remission (PR) and 10 had refractory disease (RD). Most had BEAM conditioning with a median infused cell dose of 4.84 × 106 CD 34 cells/kg. Prompt engraftment occurred in 97 patients at a median of 11days. The day 100 transplant related mortality (TRM) was 5%. At a median of 37months follow up, 79 patients are alive while 34 have relapsed. The 3-year event free survival (EFS) and overall survival (OS) are 62.3 ± 0.5% and 77.9 ± 4.4% respectively. The 3-year OS for patients in CR, PR and RD were 83.0 ± 5.2%, 78.4 ± 8.1% and 38.9 ± 1.7 respectively [p = 0.007] while the 3-year EFS for CR, PR and RD were 73.1 ± 6.2%, 61.3 ± 9.2% and 25.0 ± 1.5 respectively [p = 0.005]. Only disease status at time of ASCT was found to correlate with both OS and EFS. ASCT for HL is associated with good outcomes and low TRM. Disease status at ASCT impacted both OS and EFS and strategies to improve outcomes in patients with refractory disease needs to be explored.

Favourable outcome of patients with breast cancer brain metastases treated with dual HER2 blockade of trastuzumab and pertuzumab.

Background:Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab (TP) is a standard therapy of metastatic and localized HER2-positive breast cancer (BC), but its activity in breast cancer brain metastases (BCBM) is unknown.Methods:Patients with HER2-positive BCBM were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, therapies and overall survival (OS) were obtained. Patients were grouped into ‘TP’, ‘other-HER2-targeted therapy’ and ‘no-HER2-targeted therapy’ according to received first-line systemic therapy after diagnosis of BCBM. Radiological re-assessment of intracranial lesions was performed in patients treated with TP as systemic first-line therapy according to RANO response criteria for brain metastases (BM).Results:A total of 252 HER2-positive BC patients with BM were available for this analysis. Patients treated with TP as systemic first-line therapy after diagnosis of BM had a significantly longer OS compared with treatment with other-HER2-targeted therapy and no-HER2-targeted therapy (44 versus 17 versus 3 months, p < 0.001; log-rank test). Among radiologically re-assessed patients treated with TP as systemic first-line therapy after diagnosis of BM, 5/14 patients (35.7%) had complete intracranial remission (CR), 8/14 patients (57.1%) partial intracranial remission (PR), 1/14 patients (7.1%) stable intracranial disease (SD) and 0/14 patients (0.0%) progressive intracranial disease (PD) as best response resulting in an intracranial objective response rate (iORR) of 92.9% and an intracranial clinical benefit rate (iCBR) of 100.0%.Conclusion:First-line therapy with dual HER2-inhibition of TP after BM diagnosis was associated with the longest median OS times in patients with BCBM.

Outcomes of Autologous Hematopoietic Cell Transplantation in Diffuse Large B Cell Lymphoma Refractory to Firstline Chemoimmunotherapy

Outcomes of patients with primary refractory diffuse large B cell lymphoma (DLBCL) are dismal. The role of autologous hematopoietic cell transplant (autoHCT) in this population is not well defined in the modern era. Most data sets combine these patients with those with relapsed disease. We report the outcomes of autoHCT in patients with primary refractory DLBCL that subsequently demonstrated chemosensitive disease with salvage therapies, using the Center for International Blood and Marrow Transplant Research registry. Between 2003 and 2018, 169 patients met the inclusion criteria. The median age of the cohort was 54 years, and 64% were male. The patients had advanced stage disease (73%) at diagnosis, 27% patients had stable disease, and 73% had progressive disease after frontline chemoimmunotherapy. Following salvage therapy, 36% patients were in complete remission (CR) and 64% in partial remission (PR). Nonrelapse mortality, progression/relapse, progression-free survival (PFS), and overall survival of this cohort at 4 years were 10.8% (95% confidence interval [CI], 6% to 13%), 47.8% (95% CI, 41% to 52%), 41.4% (95% CI, 38% to 50%), and 49.6% (95% CI, 44% to 56%), respectively. On univariate analysis, patients with progressive disease after frontline chemoimmunotherapy did just as well as those with stable disease. Patients achieving CR with salvage therapy had a lower cumulative incidence of progression/relapse at 1 year (30% versus 46.9%; P=.02) and experienced superior 1-year PFS compared to patients in PR (63.2% versus 46.7%; P=.03). AutoHCT provides durable disease control and should remain the standard of care in patients with primary refractory DLBCL who respond to salvage therapies.

GCT-76. 24Gy WHOLE VENTRICULAR RADIOTHERAPY ALONE IS SUFFICIENT FOR DISEASE CONTROL IN LOCALISED GERMINOMA IN CR AFTER INITIAL CHEMOTHERAPY – EARLY RESULTS OF THE SIOP CNS GCT II STUDY

SIOP CNS GCT II aimed to establish if 24Gy Whole Ventricular Radiotherapy (WVRT) in localised germinoma is sufficient for tumour control. After central review of radiological response after ‘CarboPEI’ chemotherapy, patients in complete remission (CR) were consolidated with 24Gy WVRT. Between 2/2012 and 7/2018, 182 patients from 8 European countries with histologically-confirmed fully-staged localised germinoma were registered. 70 patients were in CR after chemotherapy, 98 in partial remission (PR), seven had stable disease, two progressive disease, and in five no response data were documented. Of the 70 patients in CR, 58 received 24Gy WVRT alone; two of these relapsed, one local and one disseminated, two and six years after diagnosis. Of the 98 patients in PR after chemotherapy, 86 received 24Gy WVRT and 16Gy boost, of which five relapsed (three local, two distant) 12–24 months from diagnosis. Twelve patients in each of the CR/PR groups received non-protocol or undocumented radiotherapy fields/doses. Median follow-up was 3.7 years. Event-free survival (EFS) for patients in CR and with WVRT only (n=58) was 98% at 4 years. 4-years EFS of patients with PR and WVRT 24Gy and 16Gy tumor boost (n=86) was 95%. Localised germinoma in CR after chemotherapy had an excellent outcome with 24Gy WVRT alone; 24GY WVRT can therefore be considered standard consolidation treatment in this group. International consensus on radiological response criteria is of utmost importance to avoid over- and undertreatment of such patients and to pave the way for further treatment reduction in this group of patients.

Prognostic Impact of Metabolic Tumor Burden in Large B-Cell Lymphoma Patients Receiving CAR T-Cell Therapy

Introduction Chimeric antigen receptor (CAR) T-cell therapy provides long-term remissions in a substantial proportion of patients with large B-cell lymphoma (LBCL) who have relapsed or are refractory (R/R) to chemoimmunotherapy. The identification of prognostic factors to identify which patients will benefit most from this therapy is crucial to improve patient selection. Even though metabolic tumor burden assessed by 18F-fluorodeoxyglucose Positron Emission Tomography (PET) has a confirmed prognostic value in the setting of chemoimmunotherapy, its predictive role after CAR T-cell therapy is not established. Methods We conducted a single-center study including all patients with R/R LBCL who received a single infusion of CD19-targeted second-generation CAR T-cells carrying a 4-1BB costimulatory domain from July 2018 to January 2020. Adverse events were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus. All patients underwent a baseline PET scan and metabolic disease evaluation after infusion. Disease response assessment was conducted according to Lugano criteria. Metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) were measured at baseline and at 1-month after CAR T-cell infusion, and correlated with disease response and development of adverse events. To identify the optimal cut-offs for metabolic parameters we used the maximally selected log-rank statistics in the PFS analysis. Results Thirty-five consecutive patients with R/R LBCL who received CAR T-cell therapy were included in the study. Patients' baseline characteristics are summarized in Table 1. Median age at treatment was 58 years, and 74% were males. At the time of diagnosis most of them had an advanced stage of disease (86%) and were refractory to the last therapy (n=31, 88%). Best response after CAR T-cell therapy included 9 (26%) patients in complete remission (CR) and 16 (46%) in partial remission (PR). Ten (28%) patients were in progressive disease (PD) at the 1-month disease evaluation. At a median follow-up of 7.6 months, median PFS and OS were 3.4 months and 8.2 months, respectively. Regarding toxicity, eleven (31%) patients developed clinically significant CAR T-cell related toxicity, defined as grade 2 or higher CRS (n=7, 20%) and grade 2 or higher ICANS (n=6, 17%). Median baseline MTV and MTV41% were 270 cm3(IQR 87-875) and 119 cm3 (IQR 32-300), respectively. Median SUVmax was 24 (IQR 17-32). Patients who responded (CR and PR) had lower baseline MTV values compared with non-responders (median of 228 cm3 vs 645 cm3, p=0.04) (Figure 1a). No association was found between MTV41% or SUVmax and disease response. In terms of PFS, a high baseline MTV (&amp;gt;82 cm3) was associated with a lower PFS compared to patients with lower MTV values (median PFS, 2.1 months vs. 6 months; HR 3.15, p= 0.02) (Table 2 and Figure 2). Patients with high baseline MTV41% values (&amp;gt;25 cm3) also had an inferior PFS (HR 3.44, p= 0.02); no association was found between baseline SUVmax and PFS (Table 2). As per OS, there was no significant association with baseline MTV, MTV41% and SUVmax (Table 2). Regarding toxicity, there was no significant association between baseline MTV, MTV 41% and SUVmax values with grade 2 or higher CRS and ICANS events (Figure 1b). All patients underwent a 1-month post-infusion PET evaluation. Disease response at this timepoint was: CR in 8 patients (23%), PR in 17 patients (49%) and PD in 10 patients (28%). For patients in CR and PR at 1-month the probability of PFS at 6 months was 62.5% and 12.7%, respectively (HR=3.89, p=0.02). For patients in PR at the 1-month evaluation, MTV values at that timepoint were predictive for PFS; patients in PR with low (&amp;lt;35 cm3) and high 1-month MTV values had a 6m-PFS of 33% and 0%, respectively (Figure 3)(HR=4.6, p = 0.01). In these patients, SUVmax values also predicted PFS and a trend towards significance was observed for MTV41% (HR=3, p=0.07). Conclusion Metabolic tumor burden parameters measured by 18FDG-PET before and 1-month after CAR-T cell infusion identify LBCL patients who benefit most from these therapies and could aid patient selection. Disclosures Iacoboni: Novartis, Gilead, Celgene, Roche: Honoraria. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp &amp; Dohme: Honoraria. Abrisqueta:AbbVie: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Speakers Bureau. Bosch:Hoffmann-La Roche: Research Funding. Barba:Novartis, Celgene, Gilead, Pfizer, Amgen, Roche: Honoraria.

Rituximab with Dose-Adjusted EPOCH (R-DA-EPOCH) with or without Autologous Stem Cell Transplantation (ASCT) As First Line Treatment in Patients with Aggressive B-Cell Lymphoma with MYC and BCL-2 and/or BCL-6 Gene Rearrangements or Increase Copy Number

Rituximab with Dose-Adjusted EPOCH (R-DA-EPOCH) with or without Autologous Stem Cell Transplantation (ASCT) As First Line Treatment in Patients with Aggressive B-Cell Lymphoma with MYC and BCL-2 and/or BCL-6 Gene Rearrangements or Increase Copy Number

Efficacy of Venetoclax Plus Hypomethylating Agent in Blast Phase Myeloproliferative Neoplasm

Introduction: Myeloproliferative neoplasms (MPN), including primary myelofibrosis (PMF), essential thrombocythemia (ET) and polycythemia vera (PV), have a propensity to evolve into blast phase myeloproliferative neoplasm (BP-MPN) with a 20-year incidence rate of 9.3 %, 3.9% and 2.6%, respectively. (Szuber et al., 2019)Treatment options for BP-MPN are limited and the prognosis of these patients is dismal with a median survival of only 3.6 months and 5-year survival rate of &amp;lt;5%.(Tefferi et al., 2018) Considering the recent reported data on the efficacy of venetoclax when combined with hypomethylating agents (HMA) in acute myeloid leukemia (AML) in both relapsed/refractory and newly diagnosed unfit patients, we have extended such combination therapy for patients with BP-MPN. Methods: We retrospectively analyzed 14 consecutive BP-MPN patients who received venetoclax plus HMA therapy between August 2018 and June 2020. We collected data regarding clinical characteristics of chronic phase MPN and BP-MPN, cytogenetic and leukemia mutation profile, efficacy and outcome. Oral venetoclax was administered in combination with azacitidine 75 mg/m2 days 1-7 (5 patients) or decitabine 20 mg/m2 days 1-5 (9 patients). Venetoclax dose was adjusted based on drug interactions particularly with azole antifungal prophylaxis. Diagnostic, risk and response assignments were according to the 2017 European LeukemiaNet (ELN) criteria.(Döhner et al., 2017) Minimal residual disease (MRD) assessment by flow cytometry, karyotype or next-generation sequencing (NGS) was performed in a subset of patients. Results: Patient characteristics at time of leukemic transformation, treatment details, response rates and overall outcome are shown in Table 1. Median age of patients was 67 years (range 48-81) with poor-risk cytogenetics in 69% of patients. JAK2 was mutated in 10 patients (71%) and CALR in 2 (14%); other mutations included TP53 in 5 patients (36%), TET2 in 4 (29%), KRAS in 3 (21%), IDH1/2 in 3 (21%), ASXL1 in 2 (14%) and U2AF1 in 2 (14%). Eight patients (57%) received venetoclax and HMA combination therapy upfront for their BP-MPN, 2 patients (14%) had failed HMA therapy previously and one patient had prior allogeneic hematopoietic stem cell transplant (AHSCT). Two patients (14%) presented with myeloid sarcoma; one of these two patients documented partial resolution of the extramedullary tumor by imaging studies, after treatment with venetoclax plus HMA. Among the remaining 12 patients, overall response rate (ORR) was 42% (n=5) and included complete remission (CR) in 3 patients (25%) and partial remission (PR) in another 2 (17%). The best response to therapy was seen after a median of 1 month (range, 1-2). Among 3 CR responders, 2 (66.6%) had minimal residual disease negative by NGS and not evidence of preceding MPN, then they successfully transitioned to AHSCT, while the third CR patient at the time of best response showed persistence of the TP53 mutation. Additionally, one PR patient subsequently relapsed and received salvage chemotherapy followed by AHSCT. (Table 2) Although data is limited by the small cohort and short follow up when the outcome of patients treated with venetoclax in combination with HMA were compared to Mayo Clinic's historical control of patients with BP-MPN treated with HMA alone (n=26) or intensive chemotherapy (n=69), there was higher CR rate in patients treated with venetoclax and HMA (25%) compared to those receiving HMA alone (4%; p=0.048) but not to those receiving intensive chemotherapy (35%; p&amp;lt;0.0001). Moreover, the intensive chemotherapy cohort showed 24% of CR with incomplete hematologic recovery (CRi) not seen in patients receiving HMA alone or HMA with venetoclax (Figure1). Conclusions: The relatively high rate of complete response observed in our patients with BP-MPN were similar to those reported in a pivotal study of elderly unfit AML patients treated upfront with venetoclax + HMA with overall response rates of 68%.(DiNardo et al., 2019) Furthermore, responders included patients with adverse molecular risk factors who usually respond poorly to conventional chemotherapy (i.e. TP53 mutated patients). Our observations provide preliminary evidence for the potential efficacy of venetoclax and HMA combination therapy in BP-MPN with the goal of achieving CR/CRi followed by consolidative AHSCT wherever possible to provide durable remission and meaningful survival benefit. Disclosures Foran: Agios: Honoraria, Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy; Xencor: Research Funding; H3Biosciences: Research Funding.

ABCL-255: Prognostic Significance of PET CT in Relapsed/Refractory Diffuse Large B Cell Non-Hodgkin Lymphoma Before Transplantation of Autologous Hematopoietic Progenitors: Experience of a Public Hospital

Context: Patients with RR DLBC NHL after first-line of treatment who undergo a salvage chemotherapy regimen and subsequent consolidation with autologous stem cell transplant have a progression-free survival (PFS) and overall survival (OS) of nearly 80% (1). The response to the second line of chemotherapy assessed by PET CT before ASCT becomes an independent prognostic factor to predict outcome (2). Objective: To analyze the results of PET CT before ASCT as a prognostic factor; to determine the PFS and OS of patients undergoing PET CT before ASCT; to compare the PFS and OS of our population to the results reported in the international literature. Design and setting: This is an observational retrospective cohort study based on the collection of information from the ASCT records of the Hospital “El Cruce” Nestor Kirchner. We included 20 patients with RR DLBC NHL who underwent PET CT prior to performing ASCT. Analysis of qualitative variables was carried out with measures of central tendency and dispersion and of quantitative variables with summary measures. Results: A large majority of patients (75%, n= 15) were in complete remission (CR) prior to ASCT. The other 25% (n=5) were in partial remission (PR). There were only 4 (20%) post-transplant relapses. In the group of patients who were in PR before ASCT, 20% (n=1) relapsed after the procedure, and this event was recorded in 20% (n=3) of those who achieved CR before ASCT. The 2-year PFS of the entire group was 83%, and the 5-year OS was 76%. The 2-year PFS for patients who had achieved CR was 80% while for patients in PR it was 80% (p=0.9). The 5-year OS of both was 76% (p=0.87). Conclusions: Even though we have not been able to establish statistically significant differences between the two groups, we have identified similar trends to those published in the international literature. Although our population of patients achieved good outcomes and there was an appropriate follow-up time, the group of patients with PR was very small, and this is probably an important bias to prove a worse outcome in that group.