Hodgkin's Lymphoma Flashcards

Question

Is more HDCT then better?

Answer 1

No JCO 2010 Andreas Josting Aim: ASCT had become standard of treatment then for relapsed HD. Investigated because the intensity of treatment needed is unclear. Hence, wanted to evaluate the impact of sequential HDCT before myelo-ablative therapy. N=240 2 groups: A) 2#DHAP --> no PD --> BEAM+ASCT B) 2# DHAP --> no PD --> sequential HD Cyclo/MTX/Etoposide --> BEAM+ASCT ``` RESULTS: 3y OS 90% vs 80% (Seq HDCT) 3y PFS 72% vs 67% 3y FFTF 71% vs 65% Significant toxicities with Seq HDCT ```

Answer 2

Milpied JCO 1996 N=1200 Retrospective study AlloBMT vs AutoBMT in relapsed HD ``` RESULTS: 4y OS 25% vs 40% (auto) 4y PFS 15% vs 25% (auto) 4y Relapse 60% vs 60% 4y non-relapse mortality 50% vs 30% (Auto) ```

Answer 3

No. Federico JCO 2003 Aim: determine if upfront ASCT should be done. N=160 4#ABVD/Doxo-containing regimens --> CR or PR --> Randomized: - HDT + ASCT - 4# conventional chemo ``` RESULTS: CR 92% (HDT+ASCT) vs 89% 5y FFS 75% vs 80% 5y OS 90% vs 90% 5y RFS 88% vs 94% ``` CONCLUSION: no benefit with HDT and ASCT

Answer 4

Antibody-drug conjugate, aka SGN-35 Chemo = Monomethyl auristatin E (MMAE) Binds to CD30 receptor Gets internalized by endocytosis, lysosomes fuse with the vesicle. MMAE is then released by cathepsin B and other lysosomal cysteine proteases. MMAE is then released in the tumor micro environment , causing cell cycle arrest and then apoptosis

Answer 5

``` Fatigue Pyre is Diarrhea Nausea Neutropenia Peripheral neuropathy ```

Answer 6

Phase I and II conducted by Anas Younes Phase II published JCO 2012 Relapsed/refractory HD after auto-SCT Historically documented CD30+ HL N=100, IV Brentuximab at 1.8mg/kg q3weekly, up to 16# RESULTS: ORR 75%, CR in 34%. Disease control rate of 96% Med time to objective response 5-6 weeks, med time to CR 12 weeks med PFS 5.6m Med duration of response for those in CR 20.5m, others 6.7m

Answer 7

Yes. AETHERA trial Moskowitz Lancet 2015 N=330 ``` Unfavorable-risk relapsed/primary refractory Classic HL S/p ASCT Then randomized into 2 arms: - Brentuximab (16# 1.8mg/kg) - Placebo ``` RESULTS: Med PFS 43m vs 24m

Answer 8

Yes. PD-1 blockade with Nivolumab Phase I study Ansell et al. N=23 Relapsed/refractory HL Heavily treated S/p Brentuximab 80% S/p ASCT 80% Received Nivolumab 3mg/kg Q2w until CR/PD or excessive toxic effects. ORR 90% CR 20% Rate of PFS at 24weeks was 90%

Answer 9

Keynote 013 Phase 1 study All failed Brentuximab 70% failed ASCT ORR 50%, CR 20%

Answer 10

``` >40yo >400 Units of cumulative dose Rapid infusion Use with other chemo agents (CDDP, cyclophosphamide, Gemcitabine) Renal insufficiency High O2 Thoracic RT Concomitant GCSF ```

Answer 11

Andreas Engert, JCO 2007 Aim: Invx if Combined modality treatment > EF-RT Combined modality = 2#ABVD-->EF-RT N=650 Stage IA to IIB with no risk factors 2 arms: A) 30Gy EF-RT + 10Gy IF-RT B) 2#ABVD --> 30Gy EF-RT+10Gy IF-RT 7y f/u RESULTS: - no difference in terms of C (95%), OS ( 90%) - FFTF significantly different 70% and 90% Conclusion --> CMT with 2# ABVD + EF-RT

Answer 12

1) Clinical staging is sufficient for stratifying early stages of the disease 2) Chemotherapy followed by IF-RT should be standard treatment 3) Duration of chemotherapy should be adapted to severity of disease

Answer 13

Ferme et al NEJM 2007 Aim: to evaluate the standard treatment for HD N=1500 15-70yo Treatment-naive, Stage I/II with favorable Prognostic and unfavorable prognostic features. 2 arms to this trial 1) H8-Favorable. Split into 2 groups: - STNI alone - 3#MOPP/ABV + IF-RT 2) H8-Unfavorable. Split into 3 groups: - 6#MOPP-ABV + IF-RT - 4#MOPP-ABV + IF-RT - 4#MOPP-ABV + STNI Prognostic factors were based on the same ones used in H7 trial. RESULTS: (Med f/u 7.5 years) (1) H8-F - 5y EFS 98% vs 74% (no chemo) - 10y OS 97% vs 92% (2) H8-U - 5y EFS 84% (6#) vs 88% (4+IF-RT) vs 87% (4+STNI) - 10y OS 88% vs 85% vs 84% CONCLUSIONS: - Early Favorable: Chemo + IF-RT should be standard of care

Answer 14

Aim: Determine if FEWER cycles of chemo and LOWER doses of RT could be delivered while maintaining high rates of disease in control in early HD with favorable prognosis ``` Stage I/II with no Risk factors, n=1400 4 arms: A) 4# ABVD + 30Gy IF-RT B) 4# ABVD + 20Gy IF-RT C) 2# ABVD + 30Gy IF-RT D) 2# ABVD + 20Gy IF-RT ``` ``` RESULTS (8y f/u): 5y FFTF 93% (4#) vs 91% (2#) Also no differences when comparing 20Gy and 30Gy CR rates across the board 96% OS 97%~, maintained at 8yrs ``` CONCLUSIONS: - No difference in efficacy btwn 2# ABVD and 4#ABVD when combined with IF-RT - In early-stage HD with favorable prognosis, 2#ABD+20Gy IF-RT is as effective and less toxic than 4# ABVD + 30Gy IF-RT

Answer 15

Karolin Behringer Lancet 2015 Done to Invx whether omission of Bleomycin +/- Dacarbazine from ABVD reduced the efficacy in the treatment of early-stage favorable HD Newly Dx, classic or Nodular LPHL N=1500 ``` 4 arms: A) 2# ABVD B) 2# ABV (Reduced intensity) C) 2# AVD D) 2# AV 30Gy IF-RT were given after 2# chemo in each group ``` RESULTS: 5y FFTF 93% (ABVD) vs 81% (ABV) vs 89% (AVD) vs 77% (AV) Conclusions: Dacarbazine cannot be omitted from ABVD without substantial loss of efficacy Bleomycin also cannot be safely omitted. Criticisms: - Because of high-event rates, assignment to AV and ABV groups stopped early - Despite differences in tumor control, no survival differences, 5y OS ~94-98% >> likely secondary to good response to 2nd line treatment.

Answer 16

Hans Eich et al JCO 2010 Aim: Invx if treatment results can be improved with more chemo and to evaluate which RT dose N=1400 ``` 16-75, newly Dx early unfavorable HL 2x2 factorial design: A) 4#ABVD + 30Gy IF-RT B) 4#ABVD + 20Gy IF-RT C) 4# baseBEACOPP + 30Gy IF-RT D) 4# baseBEACOPP + 20Gy IF-RT ``` RESULTS: 5y FFTF 85%, OS 95%, PFS 86% BaselineBEACOPP + 20Gy RT > ABVD + 20Gy RT BaselineBEACOPP +30Gy RT = ABVD + 30Gy RT ABVD + 30Gy RT uncertain if = ABVD + 20Gy RT

Answer 17

Tresckow et al JCO 2012 Aim: 4#ABVD+30Gy IF-RT gives long-term tumor control of 80%. To try and improve that with more intensive chemo N=1500 Newly Dx early unfavorable HL 2 arms: A) 4# ABVD --> 30Gy IF-RT B) 2# eBEACOPP + 2# ABVD --> 30Gy IF-RT RESULTS: 5y FFTF HR 0.4, difference of 7%. 88% vs 95% 5y PFS difference 6%, 89% vs 95% 5y OS 97%~ No overall differences in treatment-related mortality or secondary malignancies

Answer 18

Meyer NEJM 2012 Aim: to evaluate if chemo alone will suffice, as chemo+RT is a/w late treatment-related deaths N=400 Previously Untx IA/IIA A) ABVD 4-6# B) STNI - Favorable: STNI alone C) 4-6#ABVD + STNI if unfavorable ``` RESULTS: 11y f/u OS 94% (ABVD alone) s 87% (those receiving STNI) FFDP 87% vs 92% EFS 85% vs 80% ``` CONCLUSIONS: ABVD alone compared with treatment that included STNI was a/w higher rate of OS - due to lower rate of death from other causes I

Answer 19

1 - No uptake above background 2 - Uptake equal or less than that of the mediastinum 3 - Uptake > mediastinum but equal or less than that of liver 4 - Uptake moderately > liver 5 - Uptake markedly higher than liver +/- new lesions X - New areas of uptake, unlikely to be related to lymphoma

Answer 20

``` CD15+ CD30+ PAX5 weak + CD3- CD20- (majority) CD45- CD79a- ```

Answer 21

``` CD20+ CD45+ CD79a+ BCL6+ PAX5+ CD3- CD15- CD30- ```

Answer 22

Nodular sclerosis Mixed cellular laity Lymphocyte depleted HL Lymphocyte rich HL

Answer 23

1) Look out for complications of treatment - 2nd malignancies: Breast screening, low-dose C - Thyroid function if previous RT - CVS risk assessment including stress test/echo at 10-yr interval - Carotid US if neck is radiated 2) Maintain current health levels 3) General Precautions - Smoking cessation - Lifestyle management - Vaccinations - Haemophilus Pneumococcal, meningococcal, annual influenza vaccine - General cancer screening 4) Referral to survivorship clinic 5) Counselling - reproduction

Answer 24

``` IMRT Breath hold Respiratory gating Image-guided RT Proton hearty ```

Answer 25

Stage IA - IIA 1) Schlembach et al: - 5y RFS 95% and 5y OS 100% for Stage A disease treated with IFRT and regional RT alone. 2) Retrospective analysis by GHSG of 3 options in Stage IA disease: - EFRT - IFRT -Comined modality treatment CR 98% in EFRT, 95% after combined modality and 100% after IFRT. FFTF similar.

Answer 26

1) Prospective Phase II by Stanford Group - Stage I-IV s/p 4 weekly doses of Rituximab at 375mg/m2 - ORR 100%, 45% CR+uCR - median FFP 10m ``` 2) GHSG phase II Investigated Rituximab I newly Dx stage IA NLPHL CR 86%, PR 14% --> ORR 100% 3.5y OS 100% 3y PFS 80% ``` Conclusion: Rituximab alone or in combination with chemo has activity in the Mx of newly Dx and relapsed NLPHL

Answer 27

1) ISRT 30-36Gy - Stage IA, IIA (Non-bulky) 2) Observation for Stage IA disease with a completely excised solitary LN 3) Brief course of chemo + ISRT +/- Rituximab if Stage IA (bulky)

Answer 28

Chemotherapy +/- Rituximab +/- ISRT

Answer 29

1) Nodular - Atypical Lymphocytic and Histiocytic (L&H) or popcorn cells - cells embedded in a Nodular background composed of small B lymphocytes and other reactive cells 2) Diffuse - L&H cells are set against a diffuse background consisting mainly of reactive T cells ?if able to discriminate reliable. In addition, purely diffuse subtype would be classified as DLBCL or T-cell-rich B cell lymphoma.

Answer 30

CD 20+ CD15- CD30-

Answer 31

Hodgkin Reed-Sternberg cells are germinal center B cells that cannot synthesize immunoglobulin molecules

Answer 32

Patients who fail to obtain CR with initial therapy Or Those who relapse within 3 months from the end of initial therapy

Answer 33

Reappearance of HL greater than 3 months after the attainment of CR

Answer 34

B symptoms Relapse 3-12 months from end of treatment Poor response to 2nd line therapy

Answer 35

1) by IHC for latent membrane protein-1 Or 2) ISH for EBV small nuclear RNA transcripts (EBERs)

Answer 36

Infrequent in NS subtype 40% of Lymphocyte-rich HL 70% of Mixed-cellularity HL Close to 100% of lymphocyte-depleted HL

Answer 37

1) NLPHL 2) ALCL 3) DLBCL - PMBCL - T-cell rich B Cell Lymphoma 4) EBV-positive mucocutaneous ulcer

Answer 38

Radiation field includes: - clinically involved LN - adjacent, clinically uninvolved sites

Answer 39

Radiation field is limited to: | - clinically involved regions

Answer 40

RT field includes: - pre and post-chemo nodal volumes - margin of healthy tissue to accommodate uncertainties in determining the pre-chemo tumor volume

Answer 41

RT field includes: - pre- and post-chemo nodal volumes - very limited margin of healthy tissue (0.5-1cm) INRT requires optimal pre-chemo PET/CT imaging acquired with the patient in the treatment position that can be fused with post-chemo imaging

Answer 42

Santoro JCO 1987 Combined modality in the past used MOPP In attempt to reduce some of the delayed complications, ABVD was compared to MOPP in Stage IIB/IIIA/IIIB patients N=230 Tx-naiive 2 arms: 1) ABVD --> Extensive RT 2) MOPP --> Extensive RT RESULTS: - CR rate was 80% in MOPP and 90% in ABVD - 7y FFP 80% in ABVD and 60% in MOPP - 7y RFS 85% with ABVD and 75% with MOPP - 7y S 75% with ABVD and 65% with MOPP Subsequently, George Canellos published in NEJM 1992 - ABVD x 6 months = 12 months of MOPP-ABVD > MOPP

Answer 43

ABVD most efficacious George Canellos NEJM 1992 N=350 Newly dx advanced HD, Stage IIIA, IIIB, IVA, IVB Those with first relapse after RT were eligible. If no CR or who had a relapse with either MOPP or ABVD alone were switched to opposite regimen. 3 arms: 1) MOPP 6-8 cycles 2) MOPP-ABVD alternating for 12 cycles 3) ABVD 6-8 cycles RESULTS: - CR in 67% MOPP, 82% MOPP-ABVD, 83% MOPP - 5y FFS 50% MOPP, 61% ABVD, 65% MOPP-ABVD - 5y OS 66% MOPP, 73% ABVD, 75% MOPP-ABVD Conclusion: ABVD 6-8 months = 12 months of MOPP-ABVD > MOPP