Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). 1 Although 60-70% patients can be cured by the first-line immunochemotherapies such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the remaining patients show resistance to the first-line therapy or relapse after the initial response. 2,3 High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is a treatment choice for patients with relapsed or refractory (R/R) chemo-sensitive DLBCL. 4,5 Before proceeding to HDC/ASCT, several salvage chemotherapy regimens have been utilized as a bridging therapy. 5 However, there is no clear evidence showing the superiority of the specific regimen in randomized studies. For instance, a Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study, a randomized phase III trial which com-

A 62-year-old male was diagnosed with B-CLL and treated with Fludarabine-containing regimen which maintained the disease in partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed–Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline CDR3 region of the IGH gene showed that the HRS cells were clonally unrelated to the preexisting CLL cells and the HRS cells were composed of five different clones, leading to the molecular diagnosis of de novo lymphocyte-rich classic Hodgkin LPDs with SLL. Because the initial treatment was neither effective for classic Hodgkin LPDs nor for SLL, Bendamustine, Rituximab (BR) was started and complete remission was achieved, which has continued for more than one year so far. BR may be a good therapeutic option for both entities without causing hematological toxicity.

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A 62-year-old male was diagnosed with chronic lymphocytic leukemia (CLL) and treated with a fludarabine-containing regimen which maintained the disease in a partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed-Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline complementary determining region 3 (CDR3) region of the immunoglobulin heavy chain (IGH) gene showed that the Hodgkin/Reed-Sternberg cells were clonally unrelated to the preexisting CLL cells and the HRS cells were composed of five different clones, leading to the molecular diagnosis of de novo lymphocyte-rich classic Hodgkin lymphoproliferative diseases (LPDs) with small lymphocytic lymphoma (SLL). As the initial treatment was neither effective for classic Hodgkin LPDs nor for SLL, Bendamustine, Rituximab (BR) was started and complete remission was achieved, which has continued for more than one year so far. BR may be a good therapeutic option for both entities without causing hematological toxicity.

It is difficult for the elderly, those with complications, and those who live in remote areas to visit the hospital, and as a result, there are limits on the drugs they are able to use. It is therefore effective to prescribe such patients oral medications that have few adverse effects and in regimens that require few hospital visits. Clarithromycin can induce cell death by autophagy and it has a direct antitumor effect. There have been reports of the outcomes of Lenalidomide and Dexamethasone therapy with Clarithromycin which is administered orally and is safe on multiple myeloma. However, in Japan, there have been few studies. Here, we report on Clarithromycin, Lenalidomide and Dexamethasone therapy in our hospital. Method We analyzed 7 patients with relapsed refractory or refractory multiple myeloma who were treated at this hospital between January 2012 and December 2014. The Clarithromycin, Lenalidomide and Dexamethasone therapy were administered in a 28-day cycle as follows: Clarithromycin 400 mg/day for 28-days, Lenalidomide 15 mg/day for 21-days, and Dexamethasone was administered in a dose of 20 mg once per week. The response criteria used were standard International Myeloma Working Group (IMWG) Uniform Response Criteria. and adverse events were graded according to the national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) Ver. 4. Statistical analysis was performed using Easy R (EZR). Result The response to Clarithromycin, Lenalidomide and Dexamethasone therapy were selective catalytic reduction (sCR) in 2 patients, CR in 1 patient, per rectum (PR) in 3 patients, and standard deviation (SD) in 1 patient. Response rates of PR or better were observed in 86% of the patients. Duration of response was median 316-days (range, 160-522-days). Median oculus sinister (OS) period was 1,907 days. Median OS following discontinuation of the study was 1,385 days. Hematological adverse events were G1-2 anemia in 3 patients and G3-4 anemia in 1 patient. G1-2 thrombocytopenia was observed in 1 patient and G3-4 thrombocytopenia was observed in 1 patient. Leukopenia of G1-2 was observed in 6 patients but G3 was not observed. Non-hematological adverse events were G1-2 liver disorder in 6 patients, G1-2 skin rash in 3 patients, and G1-2 constipation in 2 patients. G4 adverse events were fainting and duodenal ulcer in 1 patient each. Conclusion Clarithromycin, Lenalidomide and Dexamethasone can be safely and effectively administered in the relapsed refractory multiple myeloma