강 병 욱 경북대학교병원 혈액종양내과
혈액종양내과 춘계 연수강좌
Immune-related response criteria:
Is it time to revisit?
Timeline of the development of immunotherapy
Coley WB. Ann Surg. 1891;14:199-220 Kim CJ et al. Cancer Control. 2002;9:22-30 Dudley ME et al. Science. 2002;298:850-854
Timeline of the development of immunotherapy
Coley WB. Ann Surg. 1891;14:199-220 Kim CJ et al. Cancer Control. 2002;9:22-30 Dudley ME et al. Science. 2002;298:850-854
Nature Rev Cancer. 2009;9:361-371
Timeline of the development of immunotherapy
Coley WB. Ann Surg. 1891;14:199-220 Kim CJ et al. Cancer Control. 2002;9:22-30 Dudley ME et al. Science. 2002;298:850-854
Nature Rev Cancer. 2009;9:361-371
Paradigm shift in immunotherapy
Axel Hoos et al. J immunother. 2007;30:1-15
Paradigm shift in immunotherapy
Axel Hoos et al. J immunother. 2007;30:1-15 Wolchok et al. CCR. 2009;15(23)7412-7420
Paradigm shift in immunotherapy
Paradigm shift in immunotherapy
JNCI. 2008;100(18):1280-1281
irRC
Wolchok et al. CCR. 2009;15(23)7412-7420
Quiz 1. Which of the following statements regarding the 4 response categories by irRC is false?
Quiz 2. Which of the following statements regarding the irRC is true?
irRC
irRC
irRC
ecancer. 2015;9:604
irRC
Wolchok et al. CCR. 2009;15(23)7412-7420
the sum of the products of the two largest
perpendicular diameters (SPD) of all index lesions five lesions per organ, up to 10 visceral lesions and five cutaneous index lesions
the SPD of the index lesions and of new, measurable lesions
ecancer. 2015;9:604
Quiz 3. If one patient had a 35% decrease of SPD in the total
tumor burden and a new small lesion, choose the overall response of this patient.
irRC raises several important issues.
Ribas et al. CCR. 2009;15(23):7116-7118
irRC raises several important issues.
• What would other options be?
Ribas et al. CCR. 2009;15(23):7116-7118
Ipilimumab in the treatment of metastatic MM
Hodi FS et al. NEJM. 2010;363:711 Robert C et al. NEJM. 2011;364:2517
Pembrolizumab in the treatment of metastatic MM
Robert C et al. NEJM 2015;372(26):2521-2532
Lessons from pembrolizumab study
Hamid O et al. NEJM 2013;369(2):134-144
Nivolumab in the treatment of metastatic MM
Larkin J et al. NEJM 2015;373:23-34
Nivolumab in the treatment of squamous-cell NSCLC
Brahmer J et al. NEJM 2015;373:123-135
Nivolumab in the treatment of other tumors
Motzer RJ et al. NEJM 2015;370:1803-1813
Nghiem PT et al. NEJM 2016;epub
Recent results for pembrolizumab
Hodi et al. JCO 2016;34:1510-1517
Quiz 4. What do you call the yellow-lined survival curve?
?
?
Recent results for pembrolizumab
Hodi et al. JCO 2016;34:1510-1517
Advances from 2009 to 2015
Challenges and recommendations for assessment of immunotherapy
Hoos et al. JNCI. 2010;102(18):1388-1397
Challenges and recommendations for assessment of immunotherapy
Hoos et al. JNCI. 2010;102(18):1388-1397
Immunopathological events in cancer natural history and prognosis
Girldo et al. Virchows Arch. 2015;467:127-135
Challenges and recommendations for assessment of immunotherapy
Hoos et al. JNCI. 2010;102(18):1388-1397
Challenges and recommendations for assessment of immunotherapy
Hoos et al. JNCI. 2010;102(18):1388-1397
Survival kinetics: differences between immunotherapy & conventional therapies
delayed separation statistical power reduced
• Cox regression models assume proportional hazards
after random assignment the event rates at all times will have the same ratio
Variation combinations of long-term survival and delayed effect
Chen et al. JITC. 2013;1(18):1-9
Variation combinations of long-term survival and delayed effect
Chen et al. JITC. 2013;1(18):1-9
Critical hurdles in cancer immunotherapy
Fox et al. JTM. 2011;9(214):1-13
Unidimentional measurement?
Nishino et al. CCR. 2013;19(14):3936-3943
Paradigm shift in immunotherapy
JNCI. 2008;100(18):1280-1281
Conclusion and Take Home Messages
