Light chain deposition disease involving kidney and liver in a patient with IgD myeloma.

BACKGROUND: IgD multiple myeloma (MM) is a rare subtype of MM and light chain deposition disease (LCDD) outside the kidney is also a rare and has scarcely been reported. We report herein the details of the first reported case of LCDD involving the kidney and liver co-occurring with IgD myeloma. CASE PRESENTATION: A 66-year-old female with IgD MM presented with rapidly progressive acute renal failure, ascites and pleural effusion. Immunofluorescent study of revealed the characteristic linear deposition of Igκ light chain along the glomerular and tubular basement membrane in kidney. Electron microscopy showed the powdery electron-dense deposits along the tubular and glomerular basement membrane consistent with the diagnosis of LCDD. Laser microdissection followed by mass spectrometry identified only Igκ light chain with more than 95% probability confirm the diagnosis of κ-LCDD but not heavy/light chain deposition disease. Liver biopsy with immunofluorescence study revealed the linear deposition of Igκ chain along the perisinusoidal space indicating the hepatic involvement of κ-LCDD. The patient was successfully treated with combination therapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab. CONCLUSIONS: This report emphasizes that prompt biopsy of affected organs and initiation of clone directed therapy led to the correct diagnosis and favorable outcome in patient with LCDD who has extrarenal involvement.

Real world outcomes with Bortezomib Thalidomide dexamethasone and Cyclophosphamide Bortezomib dexamethasone induction treatment for transplant eligible multiple myeloma patients in a Latin American country. A Retrospective Cohort Study from Grupo Argentino de Mieloma Múltiple.

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.

Bortezomib-containing regimens (BCR) for the treatment of non-transplant eligible multiple myeloma.

In multiple myeloma (MM) patients ineligible for transplant, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor with anti-myeloma effects, have been reported. We aimed to evaluate the impact of different bortezomib-containing regimens (BCR) for the treatment of transplant-ineligible MM. All- consecutive patients treated with BCR at our institution from 01/05 to 02/16 were evaluated. With a median of 6 cycles, an overall response rate of 95.2, 80.9, and 76.3% was observed for patients treated with cyclophosphamide-bortezomib-dexamethasone (CyBorD), bortezomib-melphalan-prednisone (VMP), and bortezomib-dexamethasone (VD), respectively (p = 0.03). The median overall survival was similar between the three different BCR, but a trend for better progression-free survival was noted in favor of CyBorD. BCR are efficacious in the treatment of transplant-ineligible MM. Patients receiving continuous therapy (CT) exhibited better outcomes, suggesting that strategies to prevent toxicity and increase the cumulative dose are warranted.

Emerging from the shadows: A rare case of gastrointestinal AL amyloidosis presenting as hematemesis.

We document a unique presentation of light chain (AL) amyloidosis in a 62-year-old man exhibiting as acute hematemesis and chronic abdominal discomfort. Esophagogastroduodenoscopy disclosed marked thickening of gastric and duodenal folds, gastroduodenal nodularity, and friable ulcerations. Biopsy confirmed amyloidosis. Subsequent investigations ratified a diagnosis of systemic AL amyloidosis with cardiac involvement. Initiation of the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen, along with tafamidis and doxycycline for cardiac pathology, led to substantial improvement of abdominal symptoms. This case highlights the variability in amyloidosis presentations and the importance of early diagnosis.

Real-world Outcomes With Cumulative Bortezomib Dose and Efficacy in the Treatment of Transplant-ineligible Multiple Myeloma With Cyclophosphamide, Bortezomib, and Dexamethasone.

BACKGROUND: Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients. PATIENTS AND METHODS: Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate. RESULTS: There was a trend for lower discontinuation rate (45.7% vs. 68.6%, P = .052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P = .035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P = .225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P = .024). There was significantly longer PFS (24.3 vs. 9.1 months, P = .012) and a trend for longer OS (22.4 vs. 61.3 months, P = .061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P = .941) and OS were similar in both groups. CONCLUSION: Higher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment.

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study.

In the primary analysis of LYRA, daratumumab + cyclophosphamide/bortezomib/dexamethasone (DARA + CyBorD) was effective and well tolerated in newly diagnosed multiple myeloma (NDMM) and relapsed multiple myeloma (RMM). We report the final analysis of LYRA (median months of follow-up: NDMM, 35.7; RMM, 35.3) after all patients completed study therapy, were followed for 36 months, or discontinued. Patients received DARA + CyBorD induction, autologous stem cell transplant (if eligible), and 12 months of daratumumab maintenance. Eighty-seven NDMM patients enrolled, 39 underwent transplant, and 63 completed maintenance. Rates of complete response or better were 48.7% and 29.8% for NDMM transplant and NDMM non-transplant patients, respectively, and 36-month progression-free survival rates were 69.3% and 72.6%. Grade 3/4 treatment-emergent adverse events occurred in 61.6% of NDMM patients. Efficacy and safety data are also reported for the smaller RMM cohort (n = 14). DARA + CyBorD followed by daratumumab maintenance was well tolerated and achieved deep, durable responses in NDMM and RMM.

Light-chain cardiac amyloidosis: a case report of extraordinary sustained pathological response to cyclophosphamide, bortezomib, and dexamethasone combined therapy.

Background: Heart involvement represents the most ominous prognostic factor in light-chain amyloidosis (AL), often foreclosing curative therapies such as high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Heart transplantation (HTx) may be considered before ASCT in rigorously selected cases of advanced AL cardiac amyloidosis (CA). In ASCT-ineligible patients, chemotherapy with cyclophosphamide, bortezomib, and dexamethasone combined (CyBorD) regimen, even at low-dose, is feasible and effective in obtaining hematological and organ response. Case Summary: A previously healthy 50-year-old woman presented with severely symptomatic new-onset heart with preserved ejection fraction, significant cardiac hypertrophy, and an 'apical sparing' pattern. Bone marrow and abdominal fat biopsy revealed AL amyloidosis due to a smouldering micromolecular λ-type myeloma with severe cardiac involvement, and the patient was judged a good candidate to HTx followed by ASCT. Despite fragile conditions, she tolerated a full course of low-dose combination therapy with bortezomib and was withdrawn from HTx list because of unexpected persistent complete hematologic response and major cardiac improvement. Disease remission was achieved in the long term (>3 years). Discussion: We report a case of exceptional persistent hematologic and cardiac response after CyBorD therapy in a patient with advanced AL-CA who left the transplantation lists (both HTx and ASCT). In ASCT-ineligible patients, chemotherapy with CyBorD regimen, even at low-dose, can lead to durable remission of the disease with excellent cardiac response.

AL Amyloidosis for Cardiologists: Awareness, Diagnosis, and Future Prospects: JACC: CardioOncology State-of-the-Art Review.

Amyloid light chain (AL) amyloidosis is a rare, debilitating, often fatal disease. Symptoms of cardiomyopathy are common presenting features, and patients often are referred to cardiologists. Cardiac amyloid infiltration is the leading predictor of death. However, the variable presentation and perceived rarity of the disease frequently lead to delay in suspecting amyloidosis as a cause of heart failure, leading to misdiagnoses and a marked delay in diagnosis, with devastating consequences for the patient. A median time from symptom onset to correct diagnosis of about 2 years is often too long when median survival from diagnosis for patients with AL amyloidosis and cardiomyopathy is 4 months to 2 years. The authors highlight the challenges to diagnosis, identify gaps in the current knowledge, and summarize novel treatments on the horizon to raise awareness about the critical need for early recognition of symptoms and diagnosis of AL amyloidosis aimed at accelerating treatment and improving outcomes for patients.

Cyclophosphamide, Bortezomib and Methylprednisolone (CyBorMe) for the Treatment of AL Amyloidosis: Initial Experience From a Single Center.

The use of cyclophosphamide, bortezomib and dexamethasone (CyBorD) is widely accepted in the treatment of AL amyloidosis (AL). Recently, the substitution of dexamethasone by methylprednisolone (CyBorMe) appeared to improve response rates and survival outcomes. All consecutive newly diagnosed AL amyloidosis treated with CyBorMe from 01/19 to 08/20 were evaluated. A historic cohort of patients treated with CyBorD was used for comparison (01/13-08/20). Methylprednisolone was given IV at 500 mg weekly for 4 weeks in the CyBorMe group. 43 patients were treated with CyBorD and 14 with CyBorMe. After a median of 4 cycles of CyBorD and 3 cycles of CyBorMe, Hematological Response was seen in 90.6% and 92.8% of cases, including CR in 28.5% and 35.7%, VGPR in 33.3% and 35.7% and PR in 30.9% and 21.4% for CyBorD and CyBorMe, respectively. Time to first response was faster in the CyBorMe group (4 vs. 6 weeks) and cardiac response was observed in 44% and 31% of patients treated with CyBorMe and CyBorD, respectively. CyBorMe appeared to be efficacious and well tolerated in patients with AL amyloidosis. Prospective studies with CyBorMe in the stage III/IV group are warranted aiming to minimize toxicity.

Cyclophosphamide-bortezomib-dexamethasone compared with bortezomib-dexamethasone in transplantation-eligible patients with newly diagnosed multiple myeloma.

Introduction: Cyclophosphamide-bortezomib-dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib-dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods: In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results: Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony-stimulating factor (gcsf). Plerixafor was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions: Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide-gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship.