Long-term toxicity of therapy for CLL. Mitchell R. Smith, M.D., Ph.D. Director of Lymphoid Malignancy Program Taussig Cancer Institute Cleveland Clinic Cleveland, OH. 1960-70s. The Evolution of Treatment Options in CLL. 1980s. 1990s. 2000s. 2010s. Purine Analogs 80% 10-20%.
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Mitchell R. Smith, M.D., Ph.D.
Director of Lymphoid Malignancy Program
Taussig Cancer Institute
The Evolution of TreatmentOptions in CLL
DESIRED Increase CR rate
ENDPOINTS: Achieve MRD status
More durable remissions
Inability to tolerate subsequent therapy
Therapy related myeloid neoplasia (t-MN)
Prolonged B- cell suppression
hypogammaglobulinemia and infection
Prolonged T- cell suppression
OTHER ORGANS FORTUNATELY NOT AN ISSUE
VACCINATIONS PNEUMOVAX, FLU, NOT ZOSTAVAX
ANTI-MICROBIALS – bacterial, viral, fungal IVIG
MYELOID GROWTH FACTORS
Rx could prevent or cause?
if same clone, as for PLL above
if different clone, as another 2nd malignancy
German CLL sg phase 2
AIHA (onset prior to Rx)2%
25 mg/m2 IV 1-5q4w × 6
Pts with previously untreated CLL requiring therapy
600 mg/m2 IV 1
20 mg/m2 IV 1-5*q4w × 6
*Patients in the FC arm received filgrastim 5 mg/kg SC
and antiviral prophylaxis
All patients received allopurinol cycle 1 and PCP prophylaxis
Flinn et al. J Clin Oncol 2007; 25:793-798
* % of cycles
Flinn I W et al. JCO 2007;25:793-798
Short term bone marrow toxicity of FC indicates additive DNA damage that will be reflected in long term toxicity
Specifically, therapy related myelodysplasia (MDS) or acute myeloid leukemia (AML)
therapy-related myeloid neoplasia (t-MN)
t-MN cases ascertained by review of E2997 case report forms and by required AdEERS reporting
Not looked for enough?
More single agent use?
Less persistent DNA damage?
*Zhou Y et al Modern Pathology 2012
Not likely to be Rx induced
Hypothesize these may be due to immunosuppression and could be influenced by therapy
(Morton LM JCO 2010)