Virtual Library

Start Your Search

Monica Ganzinelli



Author of

  • +

    MA04 - Novel Approaches with IO (ID 900)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
    • +

      MA04.06 - PD-1 Blockade Promotes Hyperprogressive Disease in NSCLC Through Macrophages Activation via Antibody-Fc/FcR Interaction (ID 12334)

      14:05 - 14:10  |  Author(s): Monica Ganzinelli

      • Abstract
      • Presentation
      • Slides

      Background

      In a subset of patients, named hyperprogressors (HPs), immunotherapy seems to paradoxically boost tumor growth. However, neither pathological and clinical features nor the underlying biological mechanism have been identified. We dissected the role of tumor-myeloid cells crosstalk as possible players.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      HPs were defined on the basis of clinical and radiological features. Baseline histological samples from patients treated with immune checkpoints inhibitors (ICI) were evaluated by immunohistochemistry for myeloid and lymphoid markers. We tested the effect on tumor growth of murine and human ICI in T-cell deficient mice injected with human lung cancer cell lines and PDXs bearing different genotypes (EGFR+, KRAS+, STK11+ and wt). Innate immune microenvironment was evaluated by FACS analysis and immunohistochemistry. In vitro studies of ICI binding functional modulation were performed in human myeloid cells from patients and healthy donors.

      4c3880bb027f159e801041b1021e88e8 Result

      In a clinical series of 187 patients treated with ICI, hyperprogression was observed in 40 (26.3%) cases. All available HP pre-treatment tissue samples (11 cases) showed CD163+CD33+PD-L1+Arginase-A1+ clustered epithelioid macrophages infiltrating the tumor foci also expressing FcRs including CD32b. No differences in T cell compartment were observed. Murine and human PD1 blocking mAbs induced a boost of tumor growth in H460 xenografs in imunocompromised mice. A similar effect was observed in EGFR+ but not in KRAS+ and wt PDXs treated with human anti-PD1. Notably, no hyperprogression was observed after treatment with murine and human anti PD-1 F(ab)2. Hyperprogressive tumors were enriched in arginase+ myeloid-macrophage cells and fibrotic features. ICI bind in vitro to human macrophages and monocytes via Fc/FcR interactions, likely involving CD32b (FcgRIIb) and triggering functional polarization.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results provide evidence that FcR triggering on macrophages by ICI delivers a signaling cascade promoting a functional reprogramming of these cells toward a more aggressive pro-tumorigenic behavior eventually inducing hyperprogression in a subset of patients with distinctive immune and genetic profile. A validation prospective study in ongoing.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA10 - Considerations in Immunotherapy / Real World (ID 911)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 105
    • +

      MA10.02 - Impact of Antibiotics on Outcome of Metastatic Non Small Cell Lung Cancer Patients Treated with Immunotherapy (ID 14021)

      10:35 - 10:40  |  Author(s): Monica Ganzinelli

      • Abstract
      • Presentation
      • Slides

      Background

      Immunotherapy (IO) is effective against metastatic non small cell lung cancer (mNSCLC). Gut microbioma has a strong impact on immune functions and its imbalance due to antibiotics (atbs) may impair the efficacy of IO. Recent works on other malignancies supported this evidence, but data are still lacking. We studied this topic in a case series of mNSCLC patients (pts) treated with IO.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data about all consecutive pts with mNSCLC treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, between 04/2013 and 01/2018 were retrospectively collected. Pts were stratified according to atb use between 1 month (mo) before and 3 mos after the beginning of IO, and to atb exposure (AEx) defined as the ratio “days under atb/days under IO”. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analysis was performed with Cox proportional model.

      4c3880bb027f159e801041b1021e88e8 Result

      One hundred fifty-seven pts were analyzed, for a median follow-up of 28.6 mos. IO consisted in an anti-PD1 agent in 62.4% of cases, in an anti-PDL1 agent in 32.5% of cases, in a combination anti-PDL1+anti-CTLA4 in 5.1% of cases. First-line IO was administered in 25 cases, second-line IO in 66 cases, third- or more advanced-line IO in 66 cases. Twenty-seven pts received atbs. The 3 most commonly used atbs were levofloxacin (55.6%), amoxicillin/clavulanate (25.9%), and ceftriaxone (14.8%). No differences in either response rate, progression free survival (PFS) and overall survival (OS) were observed between the subgroups defined by atb use (p .14, .18 and .24, respectively). Median AEx of the treated pts was 5%. The pts with an AEx longer than the median one had significantly worse PFS (2.2 vs 7.7 mos, p<.0001) and OS (4.9 vs 16.3 mos, p .0004) than the others. This result maintained significance after correction for IO line (p .0003) and performance status (p .0002), which were the only other variables influencing PFS and OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Though no differences in outcome could be observed in our population according to simple atb use, a significant disadvantage in PFS and OS became evident for pts with a higher AEx. If confirmed, these data may suggest to carefully weigh the prescription of atbs to mNSCLC pts treated with IO.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      MA10.05 - Effect of Early Steroids use in Advanced NSCLC Patients Treated with Immunotherapy (ID 14163)

      11:00 - 11:05  |  Author(s): Monica Ganzinelli

      • Abstract
      • Presentation
      • Slides

      Background

      Immunotherapy (IO) radically improved patients (pts) outcomes in advanced non-small cell lung cancer (NSCLC). Because of their immunosuppressive activity, the use of steroids as supportive care medications or for mild adverse events, even if at anti-inflammatory dosage, is debatable. In this study we assessed the effect of early steroids use on clinical outcomes of pts with advanced NSCLC treated with IO.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively collected demographics, clinical and pathological data of pts with advanced NSCLC treated with IO at our institution with at least one instrumental response assessment. Early use of steroids was defined as the use of a daily prednisone-equivalent dose 10 mg for at least 1 day within 28 days from the start of IO. Chi-square test or Fisher's exact test were used to analyze the association of early use of steroids with pts’ characteristics. The Kaplan-Meier method and the Cox proportional-hazards model were used for survival analyses while the reverse Kaplan-Meier method was used for follow-up quantification.

      4c3880bb027f159e801041b1021e88e8 Result

      We included 151 pts, 35 (23 %) of whom recurred to an early use of steroids. Six pts (4%) received combinatorial PD-L1+CTLA-4 blockade while 145 (96%) received single agent anti PD-1/PD-L1. Early use of steroids was positively associated with ≥2 metastatic sites (OR 3,08, 95% CI 1.33-7.89; P = .01) and ECOG PS 2 (OR 4.57; 95% CI 1.10-20.37; P = .03) and negatively associated with disease control (OR 0,32; 95% CI 0.14-0.71, P = .006). With a median follow-up of 28.61 months, early use of steroids characterized a poorer median OS (4.86 vs 15.14 months; HR 2.60; 95% CI 1.70-4.10; P < .0001). In the multivariable model including the only other covariate significantly associated with survival (ECOG PS), the early use of steroids was confirmed to independently worsen OS (HR 2.38; 95% CI 1.49-3.81; P = .0003). Early use of steroids was also associated with a poorer median progression-free survival (PFS) (1.98 vs 3.94 months; HR 1.80; 95% CI 1.20-2.80; P = .003).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our analysis, the early use of steroids significantly affected disease control, PFS and OS in advanced NSCLC patients treated with IO. If our findings will be further prospectively confirmed, early use of steroids should be avoided in this setting.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.01-22 - Effect of Basal Lymphopenia on Outcome of Non Small Cell Lung Cancer Patients Treated with Immunotherapy (ID 14003)

      16:45 - 18:00  |  Author(s): Monica Ganzinelli

      • Abstract
      • Slides

      Background

      The advent of immunotherapy (IO) induced profound change in treatment paradigm of metastatic non small cell lung cancer (mNSCLC). Different agents proved efficacy against the disease, leading to an improvement in patients’ (pts) survival. Nonetheless, only a minority of treated pts actually derives a benefit from IO. Some predictive factors, such as PD-L1 and tumor mutation burden, have been identified. Contradictory evidences have shown a potential negative predictive role of basal lymphopenia (BL). We investigated this topic in a retrospective cohort of mNSCLC pts.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data about all consecutive mNSCLC pts treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, between 04/2013 and 01/2018 were retrospectively collected. Pts were stratified according to lymphocyte (Lp) count at the first IO administration. BL was considered as a categorical variable, using the Institutional cutoff of 900 Lps/mL. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analysis was performed with Cox proportional model.

      4c3880bb027f159e801041b1021e88e8 Result

      One hundred fifty pts were analyzed, for a median follow-up of 28.6 mos. IO consisted in an anti-PD1 agent in 64.0% of cases, in an anti-PDL1 agent in 31.3% of cases, in a combination anti-PDL1+anti-CTLA4 in 4.7% of cases. First-line IO was administered in 23 cases, second-line IO in 66 cases, third- or more advanced-line IO in 61 cases. Median progression free survival (PFS) and overall survival (OS) of the global population were 3.2 and 11.2 months (mos), respectively. Thirty pts (20.0%) had any grade BL. These group had a significantly worse PFS (1.9 vs 3.0 mos, p.0010) and OS (4.5 vs 13.5 mos, p<.0001) than the control one. Also disease control rate (DCR) showed a significant difference in favor of non-BL pts (58.3% vs 30.0%, p.0074); response rate had a similar trend (25.0% vs 10.0%), without reaching significance (p.0881). The impact of BL on outcome remained significant after correction for the effects of performance status (p. 0045), which was the only other variable influencing OS. No factors other than BL had an influence on PFS at univariate analyses.

      8eea62084ca7e541d918e823422bd82e Conclusion

      BL had a detrimental impact on DCR, PFS and OS in our population. Given the limitations of this retrospective analysis, such results deserves confirmation in larger cases series. However, if BL was confirmed as a negative predictive factor for response to IO, it may become part of a multivariable tool to indentify the best treatment option for each pt with mNSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.