Abstract
Patients with primary refractory Hodgkin lymphoma (HL) or who relapse less than one year after completion of initial therapy will frequently respond to second line therapy. A majority of those who have a complete response (CR) to salvage therapy, and are then consolidated with high-dose chemotherapy and autologous stem cell rescue will experience prolonged relapse-free survival. It is therefore critical to identify those patients who are unlikely to respond to a given salvage regimen, so they can be given alternate treatment.
Serum thymus and activation related chemokine (TARC) is expressed by Hodgkin Reed Sternberg cells, roughly reflects tumor bulk, and decreases with treatment response among adults with HL (Plattel W, Van Den Berg A, et al., ASH, 2010). We hypothesized that the degree of reduction of serum TARC after salvage therapy would distinguish those patients with relapsed/refractory HL who go on to have a CR from those with less than a CR.
Children's Oncology Group (COG) protocol AHOD1221 was the first clinical trial to combine the antibody-drug conjugate, brentuximab vedotin (Bv), with conventional chemotherapy (gemcitabine) for children and young adults with HL. The majority (35 of 42 treated at the recommended phase 2 dose level; 83%) had primary refractory disease or very early relapse <6 months after completion of primary treatment. 27 of 40 evaluable patients experienced a CR (68%) within the first four cycles, defined by all target lesions Deauville 3 or less on FDG-PET scan (Cole et al., ASCO, 2017). 87% of CRs were observed after two cycles of therapy.
Serum was collected at the start of every cycle, and serum TARC was measured using singleplex ELISA. At baseline, 37 of 38 patients (97%) had elevated serum TARC (median 5700 pg/mL; range 379-18,667). Median serum TARC decreased to 668 pg/mL (range 6-9718; n=35; P<0.0001) after one cycle of therapy, and 368 pg/mL (range 47-1749; n=22; P<0.0001) after two cycles. 31 of 40 evaluable patients (78%) had paired serum samples collected at baseline and after one cycle of therapy. Patients who had a CR within the first four cycles of therapy showed a greater reduction in serum TARC after one cycle of therapy (median reduction from baseline = 86%; n=15) than those who did not have a CR (median 61%; n=16; P=0.03, Mann Whitney test). Six of 15 patients who had a CR showed more than a 90% reduction in serum TARC after one cycle of therapy, compared with 1 of 16 patients who did not have a CR (P=0.04, Fisher's exact test). At later time points, neither absolute serum TARC values nor reduction from baseline differed significantly between those patients with a CR and remaining subjects.
In summary, serum TARC decreases significantly from baseline after one cycle of treatment with Bv and gemcitabine among children and young adults with relapsed or primary refractory HL. Patients with a CR demonstrated a more rapid reduction in serum TARC from baseline than those who did not have a CR. This is the first report demonstrating the usefulness of TARC as a biomarker of treatment response specifically among children and young adults with HL. Future studies will test the value of altering retrieval strategy based on this early response marker.
No relevant conflicts of interest to declare.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal