Real-world data on induction therapy in patients with transplant-ineligible newly diagnosed multiple myeloma: retrospective analysis of 598 cases from Kansai Myeloma Forum.

To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.

[Systemic sarcoidosis developed after chemoradiotherapy for localized thyroid diffuse large B-cell lymphoma].

Localized thyroid diffuse large B-cell lymphoma stage with stage IE according to the Ann Arbor clinical staging system was diagnosed in a 75-year-old woman. The patient was treated with three courses of chemotherapy followed by radiotherapy. Positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) PET-CT was performed two months after chemotherapy showed increased FDG uptakes in systemic lymph nodes and gluteal muscles. Standardized uptake value in the region of interest ranged from 7.1-26.1. Since it seemed too sudden to be a recurrence, a repeat biopsy was performed from inguinal lymph nodes. Histology revealed that there were no malignant lymphoma cells but noncaseous epithelioid granuloma with multinucleated giant cells. Taken together with the findings of bilateral hilar mediastinal lymphadenopathy and elevated serum angiotensin converting enzyme (ACE) levels (32.4 U/l), sarcoidosis secondary to lymphoma was diagnosed in this patient. Subsequently, both FDG uptake and serum ACE gradually improved without any therapy. The present case strongly suggests the importance of a re-biopsy when the clinical course of recurrence is unusual.

Plateau is a prognostic factor of lenalidomide therapy for previously treated multiple myeloma.

The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.

Enhanced immune reaction resulting from co-vaccination of WT1 helper peptide assessed on PET-CT.

It has become evident that positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (FDG PET-CT) can detect anti-tumor immune response induced by various immunotherapies. To evaluate whether FDG PET-CT could detect anti-cancer immune response caused by cancer vaccine therapy, we performed a retrospective analysis of FDG PET-CT imaging of patients who were treated with Wilms Tumor 1 (WT1) vaccine therapy in Osaka University during July 2008 and June 2018. Increased FDG uptakes were detected in WT1-vaccinated skin and their draining lymph nodes during the repeated vaccination. While the FDG uptakes seemed to decrease with time after the cessation of WT1 peptide vaccinations, persistence of FDG uptakes for years in WT1-vaccinated skin were also observed in 2 cases who showed good clinical course. Moreover, the FDG uptakes of patients treated with the combination vaccine of WT1 specific cytotoxic T cell (CTL) and helper peptides were significantly stronger than of those treated with the WT1 CTL peptide alone. Since it is evident that the combination vaccine can induce a more robust anti-tumor immunity than can CTL peptide vaccine alone, the FDG uptakes in WT1-vaccinated skin might reflect the degree of immune response. These results suggest that PET-CT might be a good tool for prediction of anti-tumor immune response induced by WT1 vaccine therapy. Larger scale prospective studies therefore seem to be warranted.

[Ascending Colon Cancer with Hemophilia A Treated with Laparoscopic Right Hemicolectomy under Control of a Blood Coagulant Factor-A Case Report].

Here, we report a case of ascending colon cancer successfully treated with laparoscopic right hemicolectomy in a 74- year-old man with a medical history of hemophilia A. He was admitted to our hospital because of bloody stool and diagnosed with type 2 ascending colon cancer based on colonoscopy findings. Preoperatively, blood transfusion and administration of recombinant factor Ⅷ products were performed. Surgery involved laparoscopic right hemicolectomy plus group 3 lymph node dissection. No complications, such as bleeding, occurred during hospitalization. The patient was discharged on postoperative day 8. There have been a few reports of laparoscopic surgery for patients with hemophilia. However, this case suggests that it can be safely performed with planned factor Ⅷ supplementation in the perioperative period.

Primary Marginal Zone Lymphoma in the Posterior Mediastinum with Pleural Involvement.

We herein report a case of primary marginal zone lymphoma (MZL) of the posterior mediastinum in an 84-year-old woman. Computed tomography of the chest showed a posterior mediastinal mass in the right thoracic paravertebral region with right pleural effusion. Pathological findings of a surgical biopsy from the posterior mediastinum, along with immunohistochemical and flow cytometric results, indicated MZL. The patient was treated with chemotherapy and radiation therapy for the mediastinal lesion and achieved complete remission. A relapse occurred 3 months after the initial treatment regimen. However, a second relapse has not occurred more than 2 years after second-line chemotherapy. This is the first case of MZL originating in the posterior mediastinum.

The protective effects of lafutidine for bortezomib induced peripheral neuropathy.

Peripheral neuropathy (PN) caused by bortezomib is an important complication of multiple myeloma. Subcutaneous injection of bortezomib reduced PN, but 24% of cases were grade 2 PN and 6% of cases were grade 3 PN. PN higher than grade 2 was not resolved by subcutaneous injection. PN higher than grade 3 has serious dose limiting toxicity and is the cause of discontinuing bortezomib treatment. Lafutidine is an H2-blocker with gastroprotective activity and is thought to function by increasing mucosal blood flow via capsaicin sensitive neurons. The same activity of lafutidine is considered to improve glossodynia and taxane induced PN. We hypothesized that lafutidine prevents or improves PN that is caused by bortezomib. In the current study, bortezomib was administered in the usual manner (intravenous administration of bortezomib 1.3 mg/m(2), twice a week for 2 weeks, followed by 1 week without treatment) for up to four cycles to compare our data with other studies. Lafutidine was administered orally at a dose of 10 mg twice daily. In our eight evaluated cases, the total occurrence of PN was four out of eight patients (50%). There were only grade 1 PN (4 out of 8) cases, and no cases higher than grade 2. We conclude that (1) the total occurrence of PN was not improved, (2) there was no PN after the first course, (3) there were only grade 1 cases and there were no cases higher than grade 2, and (4) no cases discontinued bortezomib treatment because of PN. This is the first report showing that lafutidine is useful for the amelioration of bortezomib induced PN.

VNCOP-B plus rituximab therapy in elderly patients with aggressive B-cell non-Hodgkin lymphoma: a multicenter experience.

CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety. We report our clinical experience in 8 collaborative institutions to determine if the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin) combination therapy plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. Between September 2004 and December 2007, 23 previously untreated patients, median age 73 years, 50.0% classified as high-intermediate/high-risk on the standard International Prognostic Index (IPI) entered this trial. Complete remission rate was 90.5%, with a 100% overall response rate (RR) at the end of induction therapy; overall survival (OS) rate at 3 years was 76.4% (median follow-up 744 days), with an 82.6% 3-year progression-free survival (PFS) rate (median follow-up 744 days). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the patients despite prophylactic administration of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia in 30.0%, respectively. There was no treatment-related mortality (TRM). Rituximab not only combined with chemotherapy but also given sequentially improved survival. R-VNCOP-B could be another option for elderly patients who are not considered to tolerate in receiving R-CHOP.

[Five cases of de novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) achieved CR with the continuous drip infusion of low-dose etoposide and low-dose cytosine arabinoside combined with mitoxantrone (MEtA)].

From 1998 to 2001, 5 consecutive cases of AML/TMDS entered our hospital and achieved complete remission (CR) with continuous drip infusion of low-dose etoposide and low-dose Ara-C combined with mitoxantrone (MEtA regimen). The ages of the 5 patients (4 males and 1 female) ranged 32 to 50 years-old, respectively. WBCs were 1,560-45,150/microl, blasts were 12-62%. Bone marrow aspirates revealed trilineage myelodysplasia with various number of blasts. These patients had an acute onset and no preceding hematologic disorders. They were diagnosed M2/TMDS or M4/TMDS. Continuous drip infusion of etoposide (50 mg/body/day) and Ara-C (30 mg/body/day) were given for 11-14 days and a bolus injection of mitoxantrone (8 mg/m2) was added for 2-3 days. Patient 5 was given additional MIT (6.7 mg/m2 on day 6). All cases achieved CR in 21-24 days after the end of the therapy. Toxicities were nausea, vomiting, stomatitis, alopecia and fever due to infection. All were well tolerable, however. Two patients are alive more than 4 years without relapse. MEtA regimen is available for AML/TMDS.