Case 1: Mrs. MG. ANCO Hematologic Malignancies Update: Acute leukemias, MDS and myeloma

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1 Partner Logo ANCO Hematologic Malignancies Update: Acute leukemias, MDS and myeloma Tim Campbell Research Fellow UCSF Division of Hematology and Oncology September 12 th, 2015 Case 1: Mrs. MG 65 yo woman with a significant PMH of stage IIB breast cancer treated 5 years ago with mastectomy + adjuvant adriamycin/cytoxan with no recurrence Presents to PMD with 2 weeks of fatgue, easy bruising and weight loss 1

2 Case 1: Mrs. MG MedicaTons: none PMH: Breast cancer, appendicits Social History Never smoker Does not drink and no illicits Married and has 3 children Family History: Mother had early- stage breast cancer Case 1: Mrs. MG Physical Exam: Temp 37.1 BP 135/70 HR 85 Sat 98% RA Pale and fatgued appearing woman with no palpable adenopathy and no breast or chest wall masses. No hepatosplenomegaly but multple petechiae on lower legs 2

3 Case 1: Mrs. MG ANC ASH Image Bank Case 1: Mrs. MG Bone marrow biopsy: 80% myeloblasts with decreased erythroid and megakaryocyte lineages and no evidence of dysplasia Flow cytometry: blasts are CD34 + CD117 + CD138 + MPO + CD19 - TDT - CytogeneTcs: 46 XX, 5-,7- seen in 20/20 cells Molecular MutaTons: CEBPA negatve NPM1 negatve FLT3- ITD and FLT3- TKD negatve 3

4 Case 1: Discussion 65 yo woman with a history of cytotoxic chemotherapy 5 years ago, now presentng with presumed treatment- related (t- AML) What factors suggest that this is t- AML? History of breast cancer with anthracycline exposure and an appropriate latency period (median in large series is around 5 years earliest is 2-3 years) CytogeneTc changes commonly seen in series of t- AML including loss of chromosome 5 and 7 Can occur with or without preceding MDS Which primary cancers are highly associated with risk of t- AML (Smith et al. Blood 102:43-52) Hematologic: Hodgkin - > Non- Hodgkin - > Myeloma Solid: Breast - > Ovarian - > Prostate What risk is her AML? How does this affect treatment optons Poor risk given related to prior chemotherapy and adverse cytogenetc profile. If eligible, allogeneic SCT should be considered in CR1 Case 1: Outcome Mrs. MG went into remission with 7+3 inducton chemotherapy and underwent an allogeneic SCT in first remission 4

5 Case 2: Mr. TD HPI: 55 yo man with no significant PMH presents with low back pain, weight loss and fatgue Case 2: Mr. TD MedicaTons: NSAIDs as needed PMH: None Social History Former smoker Social alcohol Married Served Air Force, was never statoned overseas Family History: negatve for cancer 5

6 Case 2: Mr. TD Physical Exam: Temp 36.5 BP 150/70 HR 95 Sat 98% RA Uncomfortable on exam with significant spinal tenderness in lumbar region. No adenopathy, no hepatosplenomegaly MRI of total spine shows a large destructve soh Tssue lesion at L4 ASH Image Bank Case 2: Mr. TD Calcium 11.5 Albumin 3.3 IgG: 5 g/dl SPEP: Gamma Monoclonal band of 3g/dL IFE: IgG kappa Beta 2 microglobulin 6 mg/l Kappa light chain: 300 mg/l Lambda light chain: 20 mg/l 6

7 Case 2: Mr. TD Bone marrow biopsy: 50% plasma cells CD138 + CD38 + kappa- restricted by flow cytometry. No evidence of dysplasia CytogeneTcs: 46 XY, 17p- in 15/20 cells FISH: del (17p) Case 2: Mr. TD Received palliatve radiaton to his plasmacytoma Started systemic therapy with revlimid, velcade and dexamethasone and had a VGPR aher 3 cycles Proceeded to autologous SCT with melphalan Was started on revlimid maintenance therapy about 3.5 months aher transplant 2 months later, his SPEP showed an increase in monoclonal protein from 0.2 to 1 g/dl 7

8 Case 2 Discussion points 55 yo man with ISS stage III multple myeloma who shows evidence of early relapse aher ASCT What defines poor risk in myeloma Stage (ISS or Durie- Salmon) CytogeneTcs: 17p deleton, translocaton 4;14 or 14;16, non- hyperdiploid Early relapse aher high dose chemotherapy (less than 1 year) Gene expression profiles (investgatonal) Treatment optons for treatment failure or early relapse If less than 1 year aher ASCT, alternatve drugs than those used in inducton should be considered Role of tandem autologous stem cell transplant or allogeneic stem cell transplantaton at this Tme? Should upfront tandem autologous SCT be considered for high risk disease at diagnosis? Case 2: Outcome Mr. TD was treated with a carfilzomib- based re- inducton regimen with achievement of VGPR Underwent allogeneic SCT and normalized his serum proteins 2 months aher transplant 8

9 Case 3: Mrs. SA 72 yo woman with PMH of HTN, CAD (two stents and reduced ejecton fracton) and DM referred from her PMD for low blood counts She feels fatgue over a 6 month period and has noted some nose bleeds recently Case 3: Mrs. SA ANC ASH Image Bank 9

10 Case 3: Mrs. SA Bone marrow biopsy: prominent dysplastc features in erythroid, megakaryocytc and neutrophil lineages with 10% myeloblasts. Flow cytometry shows 12% abnormal myeloblasts CD34 + CD117 + CD38 + MPO + TDT - CD19 - CytogeneTcs: 46 XX, +8, +19, del(7q) in 15/20 cells FISH: +8, del 7q Case 3 Discussion Points 72 yo woman with significant comorbidites with myelodysplastc syndrome What defines risk in MDS (R- IPPS score) Blast percentage, anemia, thrombocytopenia, neutropenia and cytogenetc abnormalites Our patent falls into a very high R- IPSS score What are optons for upfront treatment in high- risk MDS? How about younger patents and with fewer comorbidites? HypomethylaTng agents remain primary treatment opton for patents with low- risk MDS, elderly or otherwise comorbid Allogeneic SCT is preserved upfront for younger patents with few comorbidites who have poor risk MDS 10

11 Case 3: Mrs. SA Starts on treatment with 5- azacitdine and has an inital good response with improvement in anemia and energy Aher 4 th cycle of 5- AZA, returns to clinic feeling very poor, bruising and with fevers Case 3: Mrs. SA ANC 0.9 BM biopsy: 90% myeloblasts CD38 + CD117 + MPO + TDT - CD19 - CytogeneTcs: unchanged from original MDS 11

12 Case 3 Discussion Points Now 72 yo woman with poor risk MDS transformed to acute myeloid leukemia What risk is her AML? Poor given history of MDS, complex cytogenetcs What are treatment optons? AlternaTve hypomethylatng agent, low dose cytarabine, supportve care, clinical trial If she were 60 yo and without comorbitdies? InducTon followed by allogeneic SCT would be appropriate Case 3: Outcome Mrs. SA switches to decitabine chemotherapy with a brief response and stabilized blood counts but progresses 3 months later Is not a candidate for intensive inducton chemotherapy and elects hospice 12

13 Case 4: Mr. BS 63 yo man previously very healthy and actve, presents to the emergency room with chest pain and fatgue Case 4: Mr. BS MedicaTons: none PMH: essental tremor Social History Never smoker 1-2 glasses of wine per night Married and has 2 children Family History: Paternal uncle had some type of blood cancer 13

14 Case 4: Mr. BS Physical Exam: Temp 37.5 BP 110/60 HR 85 Sat 98% RA Slightly pale but otherwise well appearing. No adenopathy, no hepatosplenomegaly Case 4: Mr. BS Blasts 69K BM biopsy: 95% myeloblasts CD33 + CD117 + MPO + TDT - CD19 - CytogeneTcs: 46 XY FISH: negatve MutaTonal profile: CEBPA negatve FLT3 ITD negatve, FLT3 TKD negatve NPM1 negatve IDH: positve mutaton in IDH1 at R132 c- kit wild- type 14

15 Case 4 Discussion Points What establishes risk categories in de novo cytogenetcally normal AML? This is partcularly important to know at relapse for clinical trials targetng these pathways Muta%on NPM1 CEBPA FLT3 ITD FLT3 TKD IDH1/2 c- kit DNMT3A non- R882 Prognos%c Value Favorable Favorable Unfavorable Controversial, beper than ITD Unfavorable but controversial Unfavorable in core binding factor altered AML (t8;21 or inv 16) Unfavorable Adapted from Walker and Marcucci. Expert Rev Hematol 5(5): Case 4: Outcome Mr. BS has intermediate risk AML and achieves remission with standard 7+3 He underwent an allogeneic SCT but unfortunately relapsed 6 months later with same IDH1 mutaton Currently enrolled in IDH inhibitor trial 15

16 Overall Summary Cases presented to highlight risk stratficaton and treatment optons in various hematologic malignancies Treatment- related AML High- risk myeloma AML arising from preexistng MDS CytogeneTcally normal de novo AML 16