1 00:00:00,040 --> 00:00:04,280 Why is it important to have specific practical guidelines on 2 00:00:04,280 --> 00:00:06,880 HIV lymphomas? Yeah, as I say, the incidence is 3 00:00:06,880 --> 00:00:11,280 decreasing, but the incidence is 4/24 higher than in general 4 00:00:11,400 --> 00:00:14,720 lymphoma population. And what is also important that 5 00:00:14,720 --> 00:00:19,440 the most frequent type of cancer in people living with HIV. 6 00:00:19,920 --> 00:00:24,120 The the lymphomas and lymphomas contribute to a significant 7 00:00:24,120 --> 00:00:27,400 morbidity and mortality to for this patient and the mortality 8 00:00:27,400 --> 00:00:30,520 rate for for lymphomas is higher than for opportunistic, 9 00:00:30,560 --> 00:00:33,640 opportunistic infections. And so there's a good reason to 10 00:00:34,040 --> 00:00:39,640 take care of these patients. Welcome to EHA Unplugged, the 11 00:00:39,640 --> 00:00:43,040 official podcast channel of the European Hematology Association. 12 00:00:43,040 --> 00:00:45,800 EHA. I am your host Isabella Rivera. 13 00:00:46,280 --> 00:00:48,400 We're here today with Professor Kai Hubel. 14 00:00:49,000 --> 00:00:50,360 Can you please introduce yourself? 15 00:00:50,920 --> 00:00:53,680 Yeah, my name is Kai Hubel. I'm a hematologist and 16 00:00:53,680 --> 00:00:57,800 oncologist from the University Hospital of Cologne in Germany. 17 00:00:58,240 --> 00:01:01,680 I'm practicing now since more than 30 years, my scientific 18 00:01:01,680 --> 00:01:05,360 interests focusing on lymphoid neoplasia, including HIV 19 00:01:05,519 --> 00:01:07,880 associated lymphomas. And I'm also sharing the 20 00:01:08,040 --> 00:01:11,640 European Network for HIV Associate Associated Lymphomas, 21 00:01:11,720 --> 00:01:16,480 which was founded last year. It is part of the EHA Lymphoma 22 00:01:16,480 --> 00:01:18,560 working Party. And we are now, we have now 23 00:01:18,560 --> 00:01:20,800 around 25 members, which is really great. 24 00:01:22,280 --> 00:01:26,600 We're here to discuss the EHA ESMO clinical practice 25 00:01:26,880 --> 00:01:29,200 guidelines on HIV associated lymphomas. 26 00:01:29,280 --> 00:01:32,360 So can you explain first what's your involvement on these 27 00:01:32,360 --> 00:01:34,600 guidelines was I'd? Let me say it was a great 28 00:01:34,600 --> 00:01:36,640 experience to develop such a guideline. 29 00:01:37,040 --> 00:01:40,120 I never thought that it needs more than two or 2 1/2 years 30 00:01:40,120 --> 00:01:43,160 from the very beginning and to getting on the guideline 31 00:01:43,160 --> 00:01:45,840 published. The first challenge was to to 32 00:01:45,840 --> 00:01:48,640 gather a group of very experienced investigators from 33 00:01:48,640 --> 00:01:51,880 different European countries. And the second challenge was to 34 00:01:51,880 --> 00:01:55,400 find a contents on the guide because I really learned that 35 00:01:56,080 --> 00:01:58,600 HIV lymphomas are treated differently in different 36 00:01:58,600 --> 00:02:01,320 European countries and we have to find a consent. 37 00:02:01,680 --> 00:02:05,240 But finally we got it published, I think it was since the summer 38 00:02:05,240 --> 00:02:08,600 last year, so. Why is it important to have 39 00:02:08,600 --> 00:02:12,280 specific practical guidelines on HIV lymphomas? 40 00:02:12,400 --> 00:02:16,280 Yeah, if you see the incidence of HIV associated lymphomas, the 41 00:02:16,280 --> 00:02:19,280 incidence is decreasing since the beginning of the century, 42 00:02:19,400 --> 00:02:22,000 mainly because of the introduction of the modern or 43 00:02:22,040 --> 00:02:25,000 combined antiretroviral therapy C ART. 44 00:02:25,440 --> 00:02:27,760 So this is a good question. Why do we need a guideline? 45 00:02:28,120 --> 00:02:31,800 But there are several reasons. First, the outcome of HIV 46 00:02:31,800 --> 00:02:35,440 associated lymphomas is different or it's worse than for 47 00:02:35,520 --> 00:02:39,440 non HIV associated lymphomas. For example, if you have a blood 48 00:02:39,440 --> 00:02:42,560 lymphoma, you can treat patients with a very intensive protocol. 49 00:02:42,800 --> 00:02:46,600 But if the patient has has Ava bloody lymphoma, then there's a 50 00:02:46,600 --> 00:02:50,320 high rate of fatalities of around 10%. 51 00:02:50,920 --> 00:02:53,320 So we need different treatment approaches. 52 00:02:53,960 --> 00:02:57,120 Another reason is that the con cumin therapies are different 53 00:02:57,120 --> 00:02:59,840 between HIV and non HIV associated lymphomas. 54 00:03:00,800 --> 00:03:05,080 Another reason is that there are rare lymphomas more or less 55 00:03:05,080 --> 00:03:08,400 exclusively developing in people living with HIV. 56 00:03:08,400 --> 00:03:10,560 For example, it's a primary funeral lymphomas and we need 57 00:03:10,560 --> 00:03:12,960 guidelines recommendations for these patients. 58 00:03:13,920 --> 00:03:17,160 And finally, we have a lot of modern treatment approaches like 59 00:03:17,160 --> 00:03:20,120 the T set directed therapies and of course we need a 60 00:03:20,120 --> 00:03:22,520 recommendation. Can we use these therapies in 61 00:03:22,520 --> 00:03:26,080 HIV infected patients? You touched a bit on this, but 62 00:03:26,080 --> 00:03:29,720 how prevalent are HIV associated lymphomas? 63 00:03:30,760 --> 00:03:33,120 Yeah, as I said before, the incidence is decreasing, but the 64 00:03:33,120 --> 00:03:37,800 incidence is 4/24 higher than in general lymphoma population. 65 00:03:38,080 --> 00:03:43,040 And what is also important that the most frequent type of cancer 66 00:03:43,520 --> 00:03:48,720 in people living with HIV is the RV lymphomas and lymphomas 67 00:03:48,720 --> 00:03:52,200 contribute to a significant morbidity and mortality to for 68 00:03:52,200 --> 00:03:54,920 this patient. And the mortality rate for for 69 00:03:54,920 --> 00:03:57,600 lymphomas is higher than for opportunistic, opportunistic 70 00:03:57,600 --> 00:04:00,640 infections. And so there's a good reason to 71 00:04:00,760 --> 00:04:03,800 take care of these patients. Which are the most common 72 00:04:03,800 --> 00:04:07,520 histological types of HIV associated lymphomas? 73 00:04:07,800 --> 00:04:11,440 The most frequent HIV HIV associated lymphomas are other 74 00:04:11,440 --> 00:04:16,279 diffuse large B cell lymphomas that accounts for about 20, 36 75 00:04:16,279 --> 00:04:21,640 or 37%, followed by the Hodgkins lymphomas with with a rate of 76 00:04:21,800 --> 00:04:27,360 26% and the Burger lymphomas with a rate of 20%. 77 00:04:27,600 --> 00:04:30,520 Is the prevalence the same as informers that are not 78 00:04:30,520 --> 00:04:32,880 associated to HIV? It's nearly the same for the 79 00:04:32,880 --> 00:04:35,880 diffuse slash B cell lymphoma but it but it's not the same for 80 00:04:35,880 --> 00:04:38,720 the burger lymphoma is more frequent and what we've rarely 81 00:04:38,720 --> 00:04:43,640 seen in HIV affected patients is the Internet lymphomas and we 82 00:04:43,640 --> 00:04:48,080 only see rare CNS lymphomas mainly because of the CRT. 83 00:04:48,640 --> 00:04:52,560 What are the main challenges in diagnosing HIV associated 84 00:04:52,560 --> 00:04:54,360 lymphomas? How do you combine the 85 00:04:54,360 --> 00:04:58,960 procedures for the diagnosis of lymphomas with the procedures to 86 00:04:58,960 --> 00:05:01,880 assess HIV? Let me say in general we can use 87 00:05:01,880 --> 00:05:06,080 the same diagnostic procedures as the use in non HIV associated 88 00:05:06,080 --> 00:05:08,640 lymphomas. But for example, there's an 89 00:05:08,640 --> 00:05:13,360 ongoing discussion about the PET CT scan, because if you use a 90 00:05:13,520 --> 00:05:17,800 PET CT in patients with HIV infections, then you may have a 91 00:05:17,800 --> 00:05:21,240 high rate of false positive results, mainly due to 92 00:05:21,240 --> 00:05:25,280 overlapping infections or due to immune disregulations, which 93 00:05:25,280 --> 00:05:28,400 should lead to an hyperplasia of the lymph nodes. 94 00:05:28,840 --> 00:05:32,040 So be careful if you use a CT scan, a PET CT scan. 95 00:05:32,080 --> 00:05:36,160 And we often use a situation that the diagnosis of the HIV 96 00:05:36,160 --> 00:05:38,000 infection is a diagnosis of the lymphomas. 97 00:05:38,000 --> 00:05:40,880 It's the same time. And in this situation, you have 98 00:05:40,880 --> 00:05:44,040 to follow for the HIV infections recommendation for newly 99 00:05:44,040 --> 00:05:47,840 diagnosed HIV infections. How do you combine the 100 00:05:47,920 --> 00:05:51,680 antiretroviral treatment for HIV with the lymphoma treatments? 101 00:05:52,200 --> 00:05:56,040 This is a very important question and there was content 102 00:05:56,040 --> 00:06:00,880 in the guideline that is no reason to stop the CRC entero 103 00:06:00,960 --> 00:06:03,840 retroviral therapy during the lymphoma treatment. 104 00:06:04,120 --> 00:06:08,200 Sometimes investigators are a little bit uncertain to continue 105 00:06:08,200 --> 00:06:12,200 the CR during lymphoma treatment because of maybe interactions, 106 00:06:12,200 --> 00:06:13,720 but there's no reason to stop it. 107 00:06:13,760 --> 00:06:16,680 Also if you use a high dose chemotherapy or not only 108 00:06:16,680 --> 00:06:20,440 transmutation or a Carkeesa therapy, does this mean that 109 00:06:20,440 --> 00:06:23,280 there is no interaction? No, there could be an 110 00:06:23,280 --> 00:06:25,360 interaction between the retroviral therapy and 111 00:06:25,360 --> 00:06:27,520 cellophoma treatment. So if you are not you are 112 00:06:27,520 --> 00:06:31,600 unfamiliar with this, you have to ask a HIV specialist or you 113 00:06:31,600 --> 00:06:33,800 can visit websites who may have you. 114 00:06:33,920 --> 00:06:36,960 But again, no reason to stop the anti retroviral therapy. 115 00:06:37,640 --> 00:06:41,360 It's dangerous to stop. It it's a very important part of 116 00:06:41,360 --> 00:06:44,640 the lymphoma therapy. We know that since we have the 117 00:06:44,720 --> 00:06:47,880 modern angioedral viral therapy available, it's a prognosis. 118 00:06:47,880 --> 00:06:49,600 It's much better for the patients. 119 00:06:50,560 --> 00:06:55,120 How do you manage the increased risk of infections on HIV 120 00:06:55,120 --> 00:06:57,880 lymphoma patients? Well, if the patient has a good 121 00:06:57,880 --> 00:07:02,560 immune system that let me say in 64 cell count of more than 200, 122 00:07:02,680 --> 00:07:05,120 you can for the same recommendation As for the HIV 123 00:07:05,120 --> 00:07:09,040 negative patients. However, if the cell count is 124 00:07:09,040 --> 00:07:13,720 less than 200, we recommend a general PCP prophylaxis and we 125 00:07:13,720 --> 00:07:17,160 also recommend an antiviral prophylaxis, especially if the 126 00:07:17,160 --> 00:07:19,600 patient has a history of a viral infection. 127 00:07:20,320 --> 00:07:23,640 And if the patient has the CD 4's hair count less than 100, we 128 00:07:23,640 --> 00:07:27,360 recommend the CMB monitoring and also we'll cause it and 129 00:07:27,360 --> 00:07:29,640 candidias as prophylaxis. So this is a little bit 130 00:07:29,640 --> 00:07:33,000 different from the HIV negative lymphomas. 131 00:07:33,240 --> 00:07:35,000 It depends a little bit on the CD 4's hair counts. 132 00:07:35,000 --> 00:07:38,520 This is about. So what are the key differences 133 00:07:38,720 --> 00:07:42,680 for you in treating an HIV positive versus an HIV negative 134 00:07:42,880 --> 00:07:45,440 lymphoma? So let me say in most situations 135 00:07:45,440 --> 00:07:48,760 we can use the same therapies for the HIV positive and HIV 136 00:07:48,760 --> 00:07:51,640 negative lymphomas, but there are some differences. 137 00:07:51,680 --> 00:07:55,000 I will give you some examples. First, the use of rituximab. 138 00:07:55,160 --> 00:07:59,920 Rituximab significantly improves the overall outcome of patients 139 00:07:59,920 --> 00:08:03,000 with B cell lymphomas and this was also shown for the HIV 140 00:08:03,000 --> 00:08:06,080 associated lymphomas. However, we know from randomized 141 00:08:06,080 --> 00:08:10,600 trials that if the patient has ACD 4 cell count less than 50 142 00:08:10,840 --> 00:08:14,560 and you use rituximab and you have a higher rate of fatal 143 00:08:14,560 --> 00:08:16,520 infections. So there's a general 144 00:08:16,520 --> 00:08:20,760 recommendation to be careful with the use of rituximab if the 145 00:08:20,760 --> 00:08:26,400 CD 4 cell count is less than 50. Another point, CAR T cells, I 146 00:08:26,400 --> 00:08:30,280 know in different European countries CAR T cells are not 147 00:08:30,360 --> 00:08:37,600 allowed in HIV lymphomas if it data are rare, but we know from 148 00:08:37,600 --> 00:08:40,440 several case reports and we know from one clinical trial 149 00:08:40,440 --> 00:08:44,440 including nearly 30 patients, CAR T cells are visible in HIV 150 00:08:44,440 --> 00:08:47,000 lymphomas. So we gave the recommendation if 151 00:08:47,000 --> 00:08:51,200 the patient has ACT 4 cell count of more than 200, then you can 152 00:08:51,200 --> 00:08:53,320 use the CAR T cells if it's in label. 153 00:08:53,320 --> 00:08:55,760 And I will briefly focus on the Burger lymphoma. 154 00:08:55,760 --> 00:08:58,360 I said at the very beginning that we have a higher fatality 155 00:08:58,360 --> 00:09:03,240 rate if you use an intensive regimen in HIV burger lymphoma. 156 00:09:03,240 --> 00:09:06,240 So if the patient is in a good condition, you may use of course 157 00:09:06,240 --> 00:09:09,400 an intensive protocol like the German female protocol or the M 158 00:09:09,400 --> 00:09:13,160 Codex IVAC protocol. However, if the patient has 159 00:09:13,160 --> 00:09:16,680 comorbidities, then you should not use these intensive 160 00:09:16,680 --> 00:09:19,080 protocols. We recommend to use something 161 00:09:19,080 --> 00:09:23,160 like those adjusted epoch R. The results are great for HIV 162 00:09:23,160 --> 00:09:26,640 burger lymphomas, but, and this is also important only if the 163 00:09:26,640 --> 00:09:30,040 patient has no CNS involvement and has no POMERA involvement. 164 00:09:30,080 --> 00:09:32,560 And you also give, as I said this, as I said at the 165 00:09:32,560 --> 00:09:36,160 beginning, give recommendations for rare lymphomas like the 166 00:09:36,160 --> 00:09:39,000 plasmoblastic lymphomas or the primary fusion lymphomas. 167 00:09:39,800 --> 00:09:43,160 So we would like to highlight that in this HA guidelines, 168 00:09:43,680 --> 00:09:48,000 there are specific and detailed recommendations for DLBCL, for 169 00:09:48,000 --> 00:09:52,080 Birkett's lymphoma, for plasma plastic lymphoma, for primary 170 00:09:52,080 --> 00:09:55,080 fusion lymphoma, for CNS lymphoma, primary and 171 00:09:55,080 --> 00:09:59,080 secondaries, for Hodgkin's lymphoma and more. 172 00:09:59,080 --> 00:10:02,720 We cannot summarize everything in this podcast, of course, so 173 00:10:02,720 --> 00:10:05,640 please check the full details in the paper in hemisphere. 174 00:10:06,640 --> 00:10:08,880 The the full link will be in the description. 175 00:10:09,360 --> 00:10:11,680 Is there anything else that we haven't touched on that you 176 00:10:11,680 --> 00:10:14,360 would like to add for the audience about these guidelines? 177 00:10:14,440 --> 00:10:17,600 I would like to to close this interview with a call because 178 00:10:17,600 --> 00:10:22,360 it's so important that we get more data on HIV lymphoma. 179 00:10:22,360 --> 00:10:27,360 So it is very important to open clinical trials for HIV, for 180 00:10:27,360 --> 00:10:30,000 patients with HIV lymphomas. It's general. 181 00:10:30,000 --> 00:10:32,480 In general, it's an exclusive criterion to have an IGV 182 00:10:32,480 --> 00:10:34,880 infection. So I don't know understand why 183 00:10:35,040 --> 00:10:37,400 please open clinical trials for HIV lymphomas. 184 00:10:37,880 --> 00:10:41,560 And 2nd, to get more data, it is necessary to have a registry and 185 00:10:41,560 --> 00:10:44,640 we have a European registry which is chaired by my colleague 186 00:10:44,640 --> 00:10:47,960 Marco Sandrich Munich. And so if you treat patients 187 00:10:47,960 --> 00:10:52,000 with HIV, inform us, please send us an e-mail or call us, and we 188 00:10:52,000 --> 00:10:54,560 will try to include your patients in the registry. 189 00:10:54,800 --> 00:10:57,400 Thank you very much, Professor Huwen, for being with us today 190 00:10:58,120 --> 00:10:58,800 It. Was my pleasure. 191 00:10:59,760 --> 00:11:01,440 And thank you to the audience for listening. 192 00:11:01,440 --> 00:11:05,200 And if you enjoyed this episode, please like it and subscribe to 193 00:11:05,200 --> 00:11:07,720 our channel. Stay tuned for more episodes of 194 00:11:07,720 --> 00:11:08,520 EH Unplugged.