Characteristics and Prognosis of Patients with Richter s Transformation of Chronic Lymphocytic Leukemia: Experience with FDG/PET

Transcription

1 Characteristics and Prognosis of Patients with Richter s Transformation of Chronic Lymphocytic Leukemia: Experience with FDG/PET Lorenzo Falchi, Long Trinh, Edith M Marom, Mylene Truong, Ellen J Schlette, Rachel L Sargent, Xuemei Wang, Susan Smith, Susan Lerner, Michael J Keating and Alessandra Ferrajoli Departments of Leukemia, Radiology, Hematopathology, and Biostatistics The University of Texas MD Anderson Cancer Center

2 No disclosures Disclosures

3 Transformed CLL: Background CLL transformation: - Richter s transformation (RT): evolution of chronic lymphocytic leukemia (CLL) into high-grade neoplasm - CLL with histologic features of increased aggressiveness (IA): grey zone FDG/PET: - powerful diagnostic/prognostic tool in most cancers - FDG-avidity (standardized uptake value, SUV) reflects tumor cell proliferation - SUV: in CLL; in RT

4 Transformed CLL: Aims Assess the characteristics of patients with transformed CLL referred to MDACC Correlate FDG/PET data, histology, and clinical outcome Evaluate the accuracy of diagnostic tools for transformed CLL

5 Transformed CLL: Methods CLL Population: CLL patients with FDG/PET scan and tissue biopsy (or BM diagnosis of transformation) 3 groups: RT, IA and chronic phase (CP) Definition of IA: increased large cells scattered/in sheets; increased (>10%) prolymphocytes Excluded: FDG/PET at a different time point concurrent cancer unless: limited ptnm, 1 year after, or remission for 5 years before FDG/PET

6 Transformed CLL: Extent of Disease (FDG/PET) Limited Extensive SUV <5 SUV 5 SUV 5 SUV 5 SUV <5 SUV 5

7 Transformed CLL: Patient Population At least 1 FDG/PET: 757 patients EXCLUDED: 376 no biopsy no PET at time of biopsy FDG/PET + LN biopsy: 381 patients EXCLUDED: 51 concurrent cancer benign histology CP histology, past RT/IA Report/SUV not available NOT YET EVALUABLE: 2 Study population: 328 patients RT: 93 IA: 116 CP: 119

8 Transformed CLL: Patient Characteristics I PARAMETER CP (119) AP (116) RT (93) No % No % No % P- value Males Untreated <.0001 Const. Symptoms ECOG PS <.0001 Bulky LNs (>5cm) Median Range Median Range Median Range Age, ys WBC, *10 3 /µl Hgb, g/dl <.0001 Plt, *10 3 /µl <.0001 LDH, U/L , , ,185 <.0001 β2-micro, mg/l <.0001

9 Transformed CLL: Patient Characteristics II P- PARAMETER CP (119) IA (116) RT (93) value No % No % No % Unmutated IGHV del17p del11q Tri Neg del13q Complex karyotype CD ZAP

10 Transformed CLL: Diagnostic PET Parameter CP (119) IA (116) RT (93) No % No % No % P- value PET prior to BX SUV bwmax, median 3.6 (0-14.3) 6.7 (0-37.8) 17.9 (0-56.3) <.0001 SUV bwmax 5* <.0001 SUV bwmax <.0001 Extensive <.0001 *Accuracy for detection of RT: SENSITIVITY 88%, NPV 91% SPECIFICITY 48%, PPV 40%.

11 Transformed CLL: Tissue Diagnosis PARAMETER CP (119) AP (116) RT (93) No % No % No % P- value Procedure.048 FNA Histology FNA + histology ND FNA* BX on SUV bwmax Ki67 max, median 10 (1-30) 32 (5-100) 70 (15-100) <.0001 * Non-diagnostic, includes benign histology or histologic downgrading

12 Transformed CLL: Treatment FIRST Regimen CP (119) AP (116) 1 R-CHOP, R-EPOCH, R-ESHAP, R-MINE, R-ICE, FCR/FCR-based; BR 2 MoAbs ± GM/HDMP/lenalidomide/cidofovir; cell therapy; anti-bcl2; vaccine therapy 3 ABVD; CNS-specific; XRT; SCT, no info on induction 4 died before therapy/evaluation; no information available RT (93) No % No % No % OFAR R-HCVAD Other chemoimmunotherapy Immunotherapy Other treatments Not evaluable Allogeneic transplant

13 Transformed CLL: Radiologic Response to First Treatment* Response AP (116) RT (93) No % No % CR PR ORR SD PD NE *Radiologic response not evaluable for patients with CP

14 Transformed CLL: Overall Survival RT, IA, CP p<.0001 Histology Total Died Survival CP mos AP mos RT mos

15 Transformed CLL: Survival by SUV p<.0001 SUV bwmax Total Died Survival < mos mos

16 Transformed CLL: Survival by Histology & SUV MAX SUV <10 MAX SUV 10 AP vs. RT, p=.62 AP vs. RT, p=.71 PHASE Total Died Survival (m) CP AP RT PHASE ToT Died Survival (m) CP AP RT

17 Transformed CLL: Survival by SUV & Extent of Disease p=.47 p=.06 EXTENT Total Died Survival Limited < mos Limited mos Extensive < mos Extensive mos

18 Transformed CLL: Cox Model for OS Baseline Characteristics (326 patients) Covariate HR 95% CI P-value Prior therapy <.0001 SUV bwmax PS Age Bulky disease (RT histology )

19 Transformed CLL: Cox Model for OS Patients with IA or RT Only (n. 208) Covariate HR 95% CI P-value Prior therapy <.0001 SUV bwmax PS Bulky disease (RT histology )

20 Survival by SUV bwmax Reduction (95 pts) p<.0001 SUV Total Died Survival <66% mos 66% NR

21 Transformed CLL: Cox Model for OS Including Response, IA or RT Only (n. 94) Covariate HR 95% CI P-value Chemosensitivity Prior therapy Bulky disease SUV bwmax (RT histology ) (PS )

22 Transformed CLL: Causes of Death 6% 16% 41% CP 37% 0% 6% 7% 21% 12% IA 54% 9% 13% 0% 7% RT 71% PD TOXICITY COMPLICATIONS UNRELATED UNKNOWN 6% SUV bwmax <10 13% 42% 32% 7% SUV bwmax 10 14% 1% 6% 10% 69%

23 Transformed CLL: Conclusions FDG/PET is important in the assessment of patients with CLL and suspected transformation FDG/PET independently predicts the risk of death of patients with transformed CLL FDG/PET identifies chemosensitive patients and may guide treatment decisions Based on the present analysis we are developing a new prognostic model for patients with CLL with IA OR RT incorporating FDG/PET