Background: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with ...daratumumab. Objectives: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. Design: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. Methods: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. Results: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β 2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. Conclusion: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.
We herein report a rare case of Burkitt lymphoma (BL) preceded by autoimmune hemolytic anemia (AIHA) caused by autoantibodies against D antigen. After a partial response to AIHA with prednisolone ...(PSL) treatment for 7 months, the patient developed BL with a t(8;22)(q24;q11.2) chromosomal translocation. Intensive immunochemotherapy, including rituximab, led to a complete response (CR) of BL; however, anti-D antibody remained detectable in the plasma and antibody-dissociated solution from erythrocytes, thus continuous therapy with PSL was necessary even after achievement of the CR. BL with AIHA is extremely rare, with only one previously reported case in the literature.
Azacitidine is the first-line therapeutic option for myelodysplastic syndrome (MDS). This report describes a case of MDS in a patient who developed fatal acute interstitial pneumonitis (AIP) after ...the first seven-day course of intravenous azacitidine (75 mg/m2/day) treatment. A review of previous and present studies of azacitidine-associated AIP suggests that azacitidine may cause life-threatening AIP during or after the first seven-day course of treatment, with pyrexia commonly preceding AIP. Although the non-hematologic adverse events associated with azacitidine are generally relatively mild, further accumulation of evidence may help to make an earlier diagnosis of azacitidine-associated AIP.
We retrospectively investigated the prognostic impact of high-risk cytogenetic abnormalities (CAs) on the outcome of treatment with bortezomib plus dexamethasone (BD) in 43 relapsed/refractory ...(Rel/Ref) multiple myeloma patients. Fluorescence in situ hybridization (FISH) analysis identified del(13q) in 25 patients, t(4;14) in 14, t(14;16) in 4, 1q21 abnormality in 12 and del(17p) in 2, while G-banding also detected chromosome 13 monosomy (−13) in metaphase spreads from 7 patients. Eighteen of 25 patients with FISH-detected chromosome 13 abnormalities also exhibited other abnormalities. Median observation period was 510 days, and median overall survival (OS) and progression-free survival (PFS) were 912 days and 162 days, respectively. Detection of del(13q), t(4;14), t(14;16) or 1q21 abnormalities by FISH and co-occurrence of chromosome 13 abnormality with other abnormalities were not associated with poorer outcomes. In contrast, detection of −13 by G-banding in metaphase spreads showed significant association with shorter OS, although the overall response rate and PFS were not inferior to those for patients without −13 detected by G-banding. BD therapy may be a potent weapon for overcoming most classical high-risk CAs, while the detection of −13 in metaphase spreads may serve as a predictor of highly progressive disease, even when treated with BD.
Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin lymphoma characterized by aggressive symptoms and various abnormal laboratory test results. One of the rare immunologic ...abnormalities in AITL is exuberant polyclonal plasmacytosis, but its clinical significance has not been evaluated. This report concerns three AITL cases with exuberant polyclonal plasmacytosis and investigates its clinical impact by comparison with 12 patients without plasmacytosis. Our study found that the performance status (PS) of the former was significantly worse and their serum immunoglobulin levels were significantly higher. All other parameters, including B symptoms, various prognostic scores, blood cell counts other than plasmacyte, and serum levels of lactate dehydrogenase, C-reactive protein and soluble interleukin-2 receptor, showed no significant differences. More importantly, although the diagnosis of AITL with plasmacytosis was not straightforward in our series, outcomes of treatment with conventional chemotherapy or immunosuppressive therapy with cyclosporine A were favorable. To conclude, AITL should be considered a candidate underlying disease of exuberant polyclonal plasmacytosis. Provided a correct diagnosis is made early and is followed by adequate treatment, the prognosis for AITL with plasmacytosis may not be worse than that for those without plasmacytosis despite the severe exhaustion at first presentation.
We report the case of a 72-year-old man who presented with non-producing multiple myeloma (MM) with three additional concomitant solid tumors that were identified by postmortem autopsy. The disease ...was refractory to anti-MM therapy including bortezomib and lenalidomide, and he finally died of bacterial pneumonia with diffuse alveolar damage 8 months after the diagnosis. An autopsy revealed that he was also affected by three other solid cancers, cholangiocellular carcinoma, medullary thyroid cancer and papillary thyroid cancer that were clinically asymptomatic and remained undiagnosed before death. A review of the literature suggests that primary quadruple cancers including MM are extremely rare.
A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high‐dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4‐year overall survival ...(OS) of patients with maintenance (n = 82) was 80%, whereas that of patients without maintenance (n = 47) was 72% (p = 0.426). The 4‐year progression‐free survival (PFS) of patients with maintenance was 38%, whereas that of patients without maintenance was 27% (p = 0.088). Multivariate analysis revealed that an International Staging System score ≥2 was associated with worse PFS (hazard ratio 1.62, p = 0.043). Among the 129 patients, two were excluded owing to early relapse, 50 patients achieved complete response (CR), and 77 patients failed to achieve CR. Patients who achieved CR showed better 4‐year PFS than those who failed to achieve CR (41% vs. 30%, p = 0.027); however, 4‐year OS was not different (76% vs. 82%, p = 0.971). In patients who achieved CR, 4‐year OS with/without maintenance was 74%/81% (p = 0.357), 4‐year PFS with/without maintenance was 42%/40% (p = 0.954). In patients who failed to achieve CR, the 4‐year OS with/without maintenance was 97%/91% (p = 0.107), and 4‐year PFS with/without maintenance was 36%/16% (p < 0.001). In patients who failed to achieve CR, maintenance significantly improved the PFS. Maintenance after HDT/ASCT can prolong PFS in patients who fail to achieve CR in real‐world settings.
Background:
Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with ...daratumumab.
Objectives:
We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status.
Design:
We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database.
Methods:
We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database.
Results:
In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen.
Conclusion:
We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.
Abstract Galectin-3 is induced in chronic myelogenous leukemia (CML) cells by co-culture with bone marrow stromal cells, making paracrine growth promotion of CML cells in conditioned medium (CM) from ...galectin-3 overexpressing CML cells more potent. We used gel filtration chromatography to demonstrate that the bovine SERPINA1-fetal bovine serum albumin (BSA) complex was specifically suppressed in CM from galectin-3 overexpressing cells. The SERPINA1-BSA complex as well as human plasma SERPINA1 inhibited the growth of CML cells, while exogenous galectin-3 partly offset this effect. These findings suggest that galectin-3 overexpression promotes paracrine growth of CML cells by interfering with the action of the growth inhibitory SERPINA1-albumin complex.
The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. ...Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy.
We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients.
According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group.
The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.
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