Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

BACKGROUND: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. METHODS: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. RESULTS: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89). CONCLUSIONS: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival.

OBJECTIVES: The long-term clinical characteristics, response to therapy, and survival in patients with immunoglobulin D (IgD) multiple myeloma (MM) were investigated. METHODS: A retrospective study was conducted that included 68 patients treated in the last 10 years, 37 of whom received bortezomib only (bortezomib group), 13 of whom received bortezomib and underwent autologous hematopoietic stem cell transplantation (bortezomib + ASCT group), and 18 of whom received conditional chemotherapy (non-bortezomib group). RESULTS: The ratio of males to females was 44:24, and the median age was 56.5 years. The overall response rate of each group was 91.9, 77.8, and 100%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 24 and 15.5 months, respectively, among the 68 patients. The median OS of each group was 23, 21.5, and 27 months, respectively. The median PFS of each group was 18, 12, and 24 months, respectively. The 3- and 5-year OS were 64 and 45%, respectively, and the 3- and 5-year PFS were 39 and 13%, respectively, among the 68 patients. Cox regression showed that the percentage of bone marrow plasmacytosis was significantly associated with OS (p = 0.038). CONCLUSIONS: The survival of IgD patients is shorter than that of other MM patients. Treatment strategies with bortezomib followed by stem cell transplantation may boost the response rate and improve survival.

Light chain multiple myeloma, clinic features, responses to therapy and survival in a long-term study.

BACKGROUND: We intended to investigate the long-term clinical characteristics, responses to therapy and survival in patients with lightchain multiple myeloma (MM). METHODS: Ninety-six patients were enrolled into the study. There were 42 κ-chain MM patients and 54 λ-chain MM patients. All the patients werestage III in the Durie-Salmonstaging system. Among them, 66 patients received Velcade (bortezomib) treatment and the other 30 did not. RESULTS: The main symptoms of these patients included bone pain (77.1%), weakness and fatigue (12.5%), foamy urine (8.3%) and extramedullaryplasmocytomas (33.3%). The overall response rate (ORR) was 95.5% in patients treated with Velcade and 60%in the patients without. The median survival times were 23 months in patients treated with Velcade and 12 months in patients without. The median time of progression-free survival (PFS) was nine months in patients treated with Velcade and five months in patients without. The one-year PFS and two-year PFS were 37% and 25%, 27% and 9% for patients treated with Velcade, or without, respectively. The three-year overall survival (OS) and five-year OS were 33% and 24%, 28% and 9% for patients treated with Velcade, or without, respectively. There was no significance in OS between the two groups (P = 0.335). But there was significant difference in PFS between the two groups (P = 0.036). CONCLUSIONS: Our long-term study demonstrated that patients with lightchain myeloma appeared to have more aggressive disease courses and poor outcomes, which could be improved by treatment with Velcade.

Clinical features and prognosis of multiple myeloma and orbital extramedullary disease: Seven cases report and review of literature.

BACKGROUND: Multiple myeloma (MM) complicated with extramedullary disease (EMD) has a poor prognosis and is a limiting factor in the treatment of MM, and no standard treatment is recommended in international guidelines. Few studies have reported MM with periorbital EMD. CASE SUMMARY: In this paper, the clinical characteristics and survival of seven patients with multiple myeloma and orbital are described and analyzed. The common ocular symptoms were blurred vision, proptosis and/or eye movement disorders, IgG type MM may be a risk factor for orbital involvement. Of them, six patients were treated with bortezomib-based regimens. The median overall survival (OS) and progression free survival for the entire cohort were 48 and 33 mo, respectively, which was much worse than the OS reported for MM patients without orbital EMD. CONCLUSION: Orbital MM may have significantly shortened survival for the entire cohort, so multidisciplinary collaboration is emphasized and recommended in the diagnosis and treatment of these difficult cases.

[Clinical Analysis of 25 Non-Transplanted Multiple Myeloma Patients Treated with Bortezomib Maintenance].

OBJECTIVE: To investigate the efficacy, survival and adverse effects of non-transplanted multiple myeloma (MM) patients treated with bortezomib maintenance. METHODS: A total of 25 newly diagnosed/relapsed non-transplanted MM patients treated in West District of Beijing Chaoyang Hospital from June 2004 to November 2015 were analyzed retrospectively. All patients received PD regimen (bortezomib and dexamethasone), including bortezomib at a dose of 1.3 mg/m2 and dexamethasone 20 mg on days 1, 8, 15, 22 in a 3-month cycle. RESULTS: Till November 1, 2017, 5 patients achieved stringent complete response (sCR), 8 patients achieved complete response (CR), 7 patients achieved very good partial response (VGPR), 4 patients achieved partial reponse (PR), while 1 patient achieved stable disease (SD). After maintenance therapy, 21 patients maintained the efficacy above PR, of which 1 patient was improved from CR to sCR; 4 patients adjusted chemotherapy after disease progressed. Median maintenance therapy was 9 cycles (range from 6 to 31), and the median maintenance time was 27 months (range from 18 to 97). Median follow-up time was 73 months (range from 25 to 171). Median progress-free survival (PFS) time was 30 months (range from 9 to 105) and overall survival (OS) time was 57 months (range from 27 to 160). Till November 1, 2019, 3-year survival rate was 84% (21/25), and 5-year survival rate was 72% (13/18). The most common adverse events were transient leukopenia, thrombocytopenia and peripheral neuropathy, which the patients could tolerate after the prevention and treatment. CONCLUSION: Bortezomib-based maintenance therapy for non-transplanted MM patients can be an option in consideration of its safety and efficacy.

Misdiagnosis of Bone Metastasis Cancer After Using Adefovir Dipivoxi in a Hepatitis B Patient with Fanconi Syndrome.

Adefovir dipivoxil is commonly used for treatment of chronic hepatitis B patients. We present a case of acquired Fanconi syndrome and hypophosphatemic osteomalacia in a patient with chronic hepatitis B who had been treated with ADV for 8 years. A 41-year-old man complained of severe bilateral hypochondrium pain and lower limb weakness, and he had the diagnosis of bone metastasis cancer or multiple myeloma. Laboratory results and radiologic findings suggested Fanconi syndrome with osteomalacia after hospitalized. For it is difficult to accurately diagnose in clinic and prone to misdiagnose, more attention should be paid to the kidney damage in the patients treated with long-term ADV.

[Clinical Analysis of Multiple Myeloma Patients Aged over 80 Years].

OBJECTIVE: To explore the clinical features, treatment response and prognosis of multiple myeloma patients aged over 80 years. METHODS: The clinical data of 23 cases of newly diagnosed multiple myeloma aged over 80 years from February 2007 to July 2014 in our hospital were analyzed retrospectively. The median age was 82, and all the patients had at least 2 complicated diseases. Only 1 patient gave up the chemotherapy because of the poor performance status, the other 22 cases received individualized treatments. Out of 23 patients, 10 received velcade containing regimen (velcade group) chemotherapy, 10 patients received melphalan containing regimen (conventional chemotherapy group) and 2 patients received lenalidomide. RESULTS: 1 patient achieved complete remission, 1 patient achieved very good partial remission, 15 patients achieved partial remission, 1 patient achieved minor remission and 4 patients had progressed. Their median survival time was 19.5 months. Their survival rate of one-year, two-years, three-years were 73.9%, 39.1%, 26.1%, respectively. The median OS time and PFS time were 21.5 (9-46) vs 13 (3-23) months (P = 0.405) and 16 (5-38) vs 10 (3-19) months in the velcade group and conventional chemotherapy group, respectively. 9 cases had been alive until December 2015, while 14 cases had died. CONCLUSION: Multiple meloma patients aged over 80 years diagnosed at advanced stage often accompanied with previous underlined diseases. Treatment should be individualized based on the evaluation of patient status. The OS and PFS time of patients could be prolonged using the velcade containing chemotherapy.

Clinical analysis of 40 multiple myeloma patients with extramedullary plasmacytoma of the head.

Objectives To investigate the clinical characteristics, survival and prognosis of patients with multiple myeloma (MM) and head extramedullary plasmacytoma (EMP). Methods Forty MM patients were enrolled in the study (18 men, 22 women; median age, 55 years). Results Median overall survival (OS) and progression-free survival (PFS) were 24 (5-78) months and 17 (2-36) months, respectively. The 2-, 3- and 5-year OS rates were 51%, 20% and 7%, respectively. The 2-year PFS was 15%. Median OS and PFS in patients administered velcade were 26 (18-50) and 22.5 (5-78) months, compared with 20 (10-30) and 13.5 (2-36) months in patients without velcade, respectively. Median OS was 23.5 (5-50) months in patients with EMP at MM diagnosis ( n = 25) and 36 (22-78) months in patients with head EMP diagnosed during the disease course ( n = 15). Sixteen MM patients had EMP invasion of the head only and 24 had invasion at multiple sites. Median OS was 25 (22-78) months in patients with EMP of the head only and 22 (5-78) months in patients with EMP invasion at multiple sites. Conclusion MM patients with head EMP show a more aggressive disease course and shorter OS and PFS. The prognosis of these patients is poor, especially in patients with head EMP at MM diagnosis, though combined chemotherapy and radiotherapy may prolong survival.

Partial remission of acute myeloid leukemia complicating multiple myeloma following COAP chemotherapy: A case report.

A 77-year-old male was admitted to hospital after complaining of fever and a cough for three days. A diagnosis of multiple myeloma was confirmed following M protein identification and a bone marrow biopsy. The patient received chemotherapy regimens of bortezomib plus dexamethasone, cyclophosphamide, thalidomide and dexamethasone, and thalidomide and dexamethasone, and was prescribed thalidomide (100 mg/d) to be taken orally for maintenance therapy. After a further two years the patient was subsequently diagnosed with acute myeloid leukemia. Chemotherapy regimens of cytarabine, aclacinomycin and daunorubicin, homoharringtonine and etoposide, and mitoxantrone and cytarabine resulted in no remission. Partial remission was obtained with a course of ifosfamide, vindesine, cytarabine and prednisone chemotherapy. This therapy may be an alternative treatment for secondary leukemia, particularly in elderly patients.