It is hard to believe we are already over halfway through the year. My how time flies when you are curing cancer! In this season's newsletter we'll bring you up to speed on what we've been been up to, from birthday celebrations and investigator-initiated clinical trials, to harnessing the immune system to fight cancer. It has been a banner year so far. 

Very exciting news on the use of targeted therapy in high-risk CLL patients was recently published by Jain et al. in The New England Journal of Medicine.The authors, which include several CLL Global grant awardees, report on an investigator-initiated phase 2 study combining ibrutinib and venetoclax therapy in previously untreated, high-risk and older patients with CLL. The results of the trial are impressive! After 12 cycles of the drug combination, all patients showed a response to treatment, with 88% of patients having a complete remission, and 61% of patients having remission with undetectable minimal residual disease. Further, there was no evidence of added toxicity when the two drugs were combined. Patients with undetectable minimal residual disease after 24 cycles of treatment will stop all therapy. Based on past studies with venetoclax, undetectable minimal residual disease should predict a long period of progression-free survival once treatment is discontinued. Having the ability to discontinue treatment for a period of time would lower the financial and side effect burdens for patients. We look forward to continued follow-up from this study to learn more about the long term efficacy of this targeted therapy. 

• On May 15, 2019, the Food and Drug Administration ( FDA) approved combination venetoclax and obinutuzumab for initial treatment of patients with CLL. This marks the second chemotherapy-free treatment option approved for patients, the first being ibrutinib. The combination reduced the risk of disease progression and death by 67% compared with obinutuzumab/chlorambucil, and also had a higher rate of minimal residual disease negativity. 

• Published in the Journal of Clinical Oncology this July, results form the phase II CLARITY trial looking at the use of ibrutinib and venetoclax in the relapsed and refractory CLL setting are encouraging. The combination was well tolerated and showed a high rate of minimal residual disease eradication, allowing some patients to stop all treatment after 12 months of combined therapy. 

• Results from Shanafelt et al., published this month in The New England Journal of Medicine, indicate that treatment with ibrutinib + rituximab is superior to standard chemoimmunotherapy in patients with previously untreated CLL. At a medium followup of 33.6 months, the phase 3 trial involving 529 patients showed favorable progression-free (89.4% versus 72.9%) and overall (98.8% versus 91.5%)  survival in the ibrutinib + rituximab treated patients as compared to the chemoimmunotherapy group. According to Dr. Shanafelt, these results are likely to "dethrone FCR as the most active chemoimmunotherapy regime against CLL."

Just because we're past the summer solstice doesn't mean it is time to slack off on using sunscreen. Patients with CLL have a compromised immune system which leads to an increased incidence in the development of other cancers (OC) , as compared to the general population, occurring at a frequency as high as 35% of patients. Skin cancer is the most common OC diagnosed in CLL patients, making year-round sun protection and skin cancer prevention a top priority. It is recommended that CLL patients have a yearly skin exam performed by a physician, and practice sun safety whenever they are outdoors. Outdoor sun safety measures includes using and reapplying sunscreen ( > SPF40), wearing a hat and sunglasses, wearing skin protective clothing, and seeking shade whenever possible. Also important for CLL patients to prevent, or catch at the earliest possible stage, OC is to stay on top of recommended cancer screenings and immunizations including the flu, pneumonia, and shingles vaccines.