Imprime PCG

Imprime PCG is an investigational immunotherapy that directly modulates neutrophils, monocytes and macrophages, enabling them to recognize and kill antibody-targeted cancer cells. In a phase 2 study presented at the ASCO Annual Meeting 2015, the activity and tolerability of imprime PCG in combination with rituximab and alemtuzumab were evaluated in 14 treatment-naive patients with high-risk CLL.9

Continue Reading

“Imprime has an interesting mechanism,” Dr Davids explained. “My sense is that it might be a way to enhance the activity of monoclonal antibodies, which I think is a worthy goal in CLL.”

Although the trial was terminated early due to slow accrual, results showed that the overall response rate was 93%, with 7 patients achieving a complete response and 2 achieving a complete response with incomplete bone marrow recovery. Grade 3 or 4 adverse events were diarrhea, transaminase increase, dehydration, gastritis, hypertension, hyponatremia, neutropenia, and febrile neutropenia.9

CD19-targeted CAR T Cells

Autologous T cells genetically modified to express CD19-targeted 19-28z chimeric antigen receptors (CARs) are being studied in a variety of hematologic malignancies, and have been found to induce durable responses in a subset of patients with relapsed/refractory CLL.10

At the ASCO Annual Meeting 2016, investigators presented an updated analysis of a phase 1 study assessing outpatient CD19-targeted CAR T cell therapy in patients with residual CLL following first-line pentostatin, cyclophosphamide, and ritximab. Eight patients achieved partial response following chemoimmunotherapy and received CAR T cells.10

After a median follow-up of 32.4 months, 2 patients achieved a complete response and a partial response each. One patient had stable disease and 1 had progressive disease. The median time to disease progression was 13.6 months. Five of 7 evaluable patients received further treatment for CLL.10

Four patients were hospitalized for pyrexia with mild cytokine release syndrome.10

“CAR T-cell therapy could eventually replace allogeneic hematopoietic cell transplantation for CLL, but I don’t see it moving up to frontline CLL therapy, as there is a fair amount of toxicity involved,” Dr Davids explained. “It is certainly not something I would put my frontline CLL patients on, but when other drugs stop working, therapeutic options with a different modality will definitely be needed.”                                       


  1. Key statistics for chronic lymphocytic leukemia. American Cancer Society website. February 23, 2016. Accessed May 20, 2016.
  2. Byrd JC, Harrington B, O’Brien S, Jones JA, Schuh A, Devereux S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:323-332.
  3. Byrd JC, Jones JA, Furman RR, Stephens DM, Devereux S, Brown JR, et al. Acalabrutinib, a second-generation bruton tyrosine kinase (Btk) inhibitor, in previously untreated chronic lymphocytic leukemia (CLL). J Clin Oncol. 2016;34(suppl; abstr 7521).
  4. O’Connor OA, Flinn IW, Patel MR, Fenske TS, Deng C, Brander DM, et al. TGR-1202, a novel once daily PI3K-delta inhibitor, demonstrates clinical activity with a favorable safety profile in patients with CLL and B-cell lymphoma. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
  5. Lunning MA, Vose J, Fowler N, Nastoupil L, Burger JA, Wierda W, et al. Ublituximab + TGR-1202 demonstrates activity and a favorable safety profile in relapsed/refractory B-cell NHL and high-risk CLL: Phase I results. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
  6. Mahadevan D, Pauli E, Cutter K, Dietz LA, Sportelli P, Miskin HP, et al. A Phase I trial of TGR-1202, a next generation once daily PI3K-delta inhibitor in combination with obinutuzumab plus chlorambucil, in patients with chronic lymphocytic leukemia. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
  7. O’Brien S, Patel M, Kahl B, Horwitz SM, Foss FM, Porcu P, et al. Duvelisib (IPI-145), a PI3K-δ,γ inhibitor, is clinically active in patients with relapsed/refractory chronic lymphocytic leukemia. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 6-9, 2014; San Francisco, CA.
  8. Reiff SD, Guinn D, Mantel R, Smith L, Cheney C, Johnson AJ, et al. Evaluation of the novel Bruton′s tyrosine kinase (BTK) inhibitor GDC-0853 in chronic lymphocytic leukemia (CLL) with wild type or C481S mutated BTK. J Clin Oncol. 2016;34(suppl; abstr 7530).
  9. Bose N, Zent C, Weiner GJ, LaPlant B, Ottoson N, Leonardo S, et al. A phase (Ph) 1/2 trial of rituximab (RX), imprime PGG (IP), and alemtuzumab (AL) in the early treatment of patients (Pts) with high risk chronic lymphocytic leukemia (CLL). J Clin Oncol. 2015;33(suppl;abstr 7078).
  10. Geyer MB, Park JH, Riviere I, Wang X, Purdon T, Sadelain M, et al. Updated results: phase I trial of autologous CD19-targeted CAR T cells in patients with residual CLL following initial purine analog-based therapy. J Clin Oncol. 2016;34(suppl; abstr 7526).