[ROQs] Heme, HL & NHL Flashcards by Muneeb Khan

What are the favorable vs. unfavorable risk factors for early-stage lymphoma per different study groups?

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What are the favorable vs. unfavorable risk factors for early-stage lymphoma per the GHSG?

Favorable: No risk factors
Unfavorable: ≥ of the following:
– ESR > 50 and no B sx
– ESR > 30 w/ B sx
– Mediastinal mass-intrathoracic diameter > 0.33
– ≥ 3 nodal sites
– Any extranodal lesion
Only risk stratification system to include >2 nodal sites any EN lesions
– The others exclude EN lesion criteria, and usually require >3 nodal sites

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What is the classical Ann Arbor Staging for Lymphoma?

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How are LN regions categorized for staging purposes per Ann Arbor, EROTC, and GHSG?

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What is the current Lugano Staging for Lymphoma?

Limited
– Stage I: one node or group of nodes
— Stage IE: single extra-lymphatic site in the absence of nodal involvement
– Stage II: two or more nodal groups, same side of the diaphragm
— Stage IIE: contiguous extra-lymphatic extension from a nodal site with or without the involvement of other lymph node regions on the same side of the diaphragm.
Advanced
– Stage III
– Nodes on both sides of the diaphragm
– Nodes above the diaphragm with spleen involvement
— Stage III(1): involvement of the spleen or splenic, hilar, celiac, or portal nodes
— Stage III(2): involvement of the para-aortic, iliac, inguinal, or mesenteric nodes
– Stage IV: diffuse or disseminated involvement of one or more extranodal organs or tissue beyond that designated E, with or without associated lymph node involvement
Further Classifiers:
– Absence (A) or presence (B) of B Sx
– (E) refers to extranodal contiguous extension that can still be encompassed within an irradiation field appropriate for nodal disease of the same anatomic extent (if more extensive than that, label as IV)
– (bulky) if a single nodal mass >10 cm or >1/3 of transthoracic diameter

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What is considered limited vs. extensive stage HL?

Limited: Stage I-II, non-bulky
Extensive: Everything else

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What is the tx paradigm for favorable stage I/IIA classic HL?

Combined CRT
– ABVD ×2–4C and ISRT to 20-30 Gy
CHT Alone
– ABVD ×3–4C (if PET-negative after 2–3C, i.e., Deauville 1–2)
– Stanford V × 8 weeks + ISRT to 30 Gy

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What is the tx paradigm for unfavorable stage I/II classic HL?

CRT
– ABVD ×4C + ISRT 30 Gy
– BEACOPP x2C + ABVD x2C + ISRT 30 Gy
– Stanford V × 12 weeks + ISRT 30 to 36 Gy
CHT Alone:
– ABVD × 6C

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What is the tx paradigm for stage III/IV Classic HL?

ABVD ×6C
– Consider ISRT to initially bulky or select PET + sites
Escalated BEACOPP × 6C

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What is the current tx paradigm stage I-II NLPHL?

Stage I/IIA, fav → resection f/b obs. vs. ISRT alone
– R0 resection → Obs
– < 5 cm → 30 Gy
– > 5 cm → 36 Gy
Stage IA/IIA bulky or IB/IIB, unfav
– Chemo → ISRT
— R-CHOP, R-ABVD, R-CVP
— R included as NLPHL is CD20+

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What is the current tx paradigm for Stage III-IV NLPHL?

Chemo ± ISRT
– R-CHOP, R-ABVD, R-CVP
— R included as NLPHL is CD20+
OR local RT for palliation only

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Which CHT drugs comprise the ABVD regimen?

ABVD:
- doxorubicin (Adriamycin)
- Bleomycin
- Vinblastine
- Dacarbazine)

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Which CHT drugs comprise the BEACOPP regimen?

BEACOPP
- Bleomycin
- Etoposide
- Doxorubicin (Adriamycin)
- Cyclophosphamide
- Vincristine (Oncovin)
- Procarbazine
- Prednisone

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Which CHT drugs comprise the Stanford V regimen?

Mnemonic: BE A VVPN
– Bleomycin
– Etoposide
– Doxorubicin (Adriamycin)
– Vinblastine
– Vincristine
– Prednisone
– Nitrogen mustard

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Which CD markers are +ve in the classic Reed-Sternberg HL cells?

CD15+
CD30+

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What is the Deauville score?

The Deauville Score is used to grade PET/CT response of individual lymphoma lesions:
– 1: No uptake
– 2: Uptake ≤ mediastinum
– 3: Mediastinum < uptake < liver
– 4: Uptake moderately > liver
– 5: Uptake markedly > liver or presence of new lesions
– X: Not attributed to lymphoma

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Which Deauville scores are considered -ve and which are considered +ve per HD16 trial?

Negative: 1-2
Positive: 3-5

What is the purpose of EORTC H10?

F and UF stage I-II HL
– Evaluate the role of RT in PET- disease post-ABVD x2C

What are the pt population, randomization, and endpoint of EORTC H10?

Pts: Fav and Unfav. stage I-II HL
Randomization: ABVD x2 f/b PET f/b
– 🏆 Standard, non-PET directed tx:
— ABVD (x1C for F, x2C for UF)
— 30-36 Gy INRT
– PET directed INRT:
— PET-: additional ABVD (total x6C for UF, total x4C for F)
— PET+: BEACOPP x2C + 30-36 Gy INRT
Primary endpoint: PFS noninferiority

What are the results of EORTC H10?

Overall:
– CR Rate 86%
– Unfav. CR rate 75%
– PFS improved in standard arms vs. directed arms.
– OS NS.
Fav + PET-: ABVD x 3C + INRT vs. ABVD x 4C:
– 5-yr PFS 99% vs. 87%
– 10-yr PFS 99% vs. 85%, superior
– 10-yr OS 100% vs. 98%, NS
– 10-yr 2nd cancer 4.0% vs. 3.8%
Unfav. + PET-: ADVD x4C + INRT vs. ABVD x6C:
– 5-yr PFS 92% vs. 90%
– 5-yr OS 100% in both arms
– 10-yr PFS 91% vs. 86%, not non-inferior
– 10-yr OS 95%, NS
– 10-yr 2nd cancer 6.8% vs. 6.5%
– With ABVD alone, 73% of failures were at original sites
PET+: ABVD+INRT vs. BEACOPPesc+INRT
– 5-yr PFS 77% vs. 91%
– 10-yr PFS 79% vs. 85%
No difference in 10-yr toxicity or 2nd cancer

What are the conclusions of EORTC H10?

Overall:
- SOC for fav. early stage HL is ABVC x2C + IFRT to 20 Gy

More granularly:
- Observation is not non-inferior to INRT in fav. and unfav. early-stage HL with negative PETs after chemo
– PFS with INRT was superior in fav. PET negative
– Additional cycles of chemotherapy cannot replace INRT in this setting.
- No OS benefit to INRT, but INRT spares some from salvage therapy
- In PET-positive lymphoma, BEACOPPesc improves PFS over ABVD

What were the results of the German HD10 study for classic HL?

Early-stage favorable (german criteria) HL
Randomization: 2/2 → ABVD x 2C vs. 4C and INRT 20 Gy vs. 30 Gy
Results: ABVD x4C + 30 Gy vs. ABVD x2C + 20 Gy
– 10-yr PFS: ~88% for both (NS)
Conclusion: ABVD x 2C + IFST 20 Gy is standard for early-stage fav. HL

What was the purpose of the German HD14?

To see if tx intensification would help in pts w/ HL w/ ≥ 1 GHSG unfav. risk factor

What are the pt population, randomization, and endpoint of the German HD14?

Pt Population
– Stage IA-IIB with at least one unfavorable GHSG risk factor
Randomization:
– escBEACOPPx2 + ABVDx2 + IFRT 30 Gy
– ABVD x4 + IFRT 30 Gy
Endpoint(s): FFTF and PFS

What are the results of the German HD14?

- (escBEACOPPx2 + ABVDx2 + 30 Gy IFRT) vs. (ABVD x4 + 30 Gy IFRT) -- 5-yr FFTF 95% vs. 88% (p=0.0451) --- on subanalysis, benefit only in bulky or B sx -- 5-yr PFS 95.4% vs. 89.1% (p = ss). -- 5-yr OS ~97% both -- CR ~95% both -- Relapses 3% vs. 8% -- Acute toxicity increased w/ esc tx -- Late toxicity not different

Which CD markers are +ve in the NLPHL cells?

- CD20+ - CD15- - CD30- ## Footnote CD20+ → use Rituximab in CHT regimens

What is the main interpretation of German HD14?

- BEACOPP/ABVD + IFRT improves FFTF and PFS over ABVD + IFRT in unfavorable HL - BEACOPP/ABVD is not routinely used in the US 2/2 increased toxicity - ABVD arm delivered only 4C. For pts w/ unfav. risk factor(s), practitioners in the US use 6C

What are the results of the German HD11?

- Unfavorable HL -- Stage I or IIA, with ≥1 risk factor: large MS mass, extranodal disease, elevated ESR, ≥3 nodal regions -- Stage IIB with increased ESR or ≥3 nodes - Randomization: 2x2 1. escBEACOPP x4 vs. 🏆 ABVD x4 2. 🏆 IFRT 30 Gy vs. 20 Gy - Results: -- ABVD + 30 Gy, BEACOPP + 20 Gy, and BEACOPP + 30 Gy are noninferior --- 5-yr OS ~95%, 5-yr PFS ~88% -- ABVD 20 Gy is not noninferior --- 10-yr PFS 76% vs. 84% vs. in other arms -- BEACOPP is more toxic than ABVD, and 30 Gy is more toxic than 20 Gy - Conclusion — ABVD + 30 Gy and BEACOPP + 20 Gy are preferred treatment options for unfavorable HL.

What is the purpose of the German HD16?

To determine whether patients with favorable responses to chemotherapy can skip IFRT in early-stage favorable HL

What are the pt population, randomization, and endpoint of the German HD16?

- Pt population: -- HL Stage I-II, favorable -- *NLPHL allowed* - Randomization: ABVD x2 → PET Scan -- Non-PET directed IFRT: 20 Gy -- PET-directed IFRT: --- PET+: 20 Gy IFRT --- PET-: no RT - Primary EP: PFS noninferiority

What are the results and the conclusion of the German HD16?

- IFSRT vs. no RT for PET- pts -- 5-yr OS 98% both arms -- 5-yr PFS 93% IFRT vs. 86% no RT -- In-field recurrence 2% vs. 11% -- Out-field recurrence, 4-7% in both arms - Conclusion: -- IFRT cannot be omitted even in patients with negative PET after chemotherapy.

What are the B symptoms for lymphoma?

Lymphoma B-sx: - Unexplained fevers > 38 °C - >10% weight loss over the last 6 mos - Drenching night sweats

What is the main conclusion of the German HD7 trial?

- HD7 shows that ABVD x 2C + EFRT is more effective than EFRT alone for favorable early-stage HL -- Improves freedom from treatment failure but NOT OS

What is the current recommended course of action for refractory HL?

- Bx confirmation - 2nd line CHT, like ICE

Brentuximab vedotin targets which cell membrane protein?

- CD **3**0 -- Mnemonic: **3**rentuximab - A/w neuropathy - Used for advanced stage and refractory/relapsed HL - Used as an early consolidation therapy after ASCT

Which trials were included in the Cochrane MA for the tx of early-stage HL, and what were the main takeaways from this MA?

- 7 trials (CALGB 7751; EORTC-GELA H9-F; EORTC H10U/H10F; Mexico B2H031; Memorial Sloan-Kettering trial #90-44, UK NCRI RAPID, HD6) - Main takeaways: Addition of RT to CHT -- Doesn't impact OS --- However, when looking only at pts who received RT as planned, it improves OS (p<0.0001) -- Improves PFS (p=0.001)

Which subtype of HL has the greatest chance of transforming into DLBCL?

NLPHL ## Footnote Remember, you use R in CHT regimens for NLPHL cuz it is CD20+. It shares this feature w/ DLBCL so it makes sense!

Are BMBx routinely done as part of the lymphoma staging?

No, BMBx are no longer routinely indicated

Which type of HL can be treated w/ ISRT alone w/o CHT?

Stage I/II A NLPHL

What were the findings of the German HD 0607 trial for HL?

- IIB-IVB, bulky (≥5 cm) HL s/p ABVD x6C w/ -ve (D1-3) PET2 and PET6 → Consolidative RT (30 Gy in 18-20 fractions) vs. obs -- 6-year PFS NS in any size subgroups -- Subgroup A (5-7 cm): 91% vs. 95% (NS) -- Subgroup B (8-10 cm): 98% vs. 90% (NS) -- Subgroup C (>10 cm): 89% vs 86% (NS)- Conclusion: - Pts w/ bulky disease s/p ABVD x6C w/ metabolic CR may not benefit from consolidative RT. - Those with only metabolic PR may benefit from consolidation (EORTTC 20884)